Python Exercises PDF

Bioinformatics Programming 2013
Problem 1
Installing Python
Why Python?
Rosalind problems can be solved using any programming language. Our language
of choice is Python. Why? Because it's simple, powerful, and even funny. You'll
see what we mean.
If you don't already have Python software, please download and install the appropriate version for
your platform (Windows, Linux or Mac OS X). Please install Python of version 2.x (not 3.x) — it has
more libraries support and many well-written guides.
After completing installation, launch IDLE (default Python development environment;; it's usually
installed with Python, however you may need to install it separately on Linux).
You'll see a window containing three arrows, like so:
>>>
The three arrows are Python's way of saying that it is ready to serve your every need. You are in
interactive mode, meaning that any command you type will run immediately. Try typing 1+1 and
see what happens.
Of course, to become a Rosalind pro, you will need to write programs having more than one line.
So select File → New Window from the IDLE menu. You can now type code as you would into a
text editor. For example, type the following:
print "Hello, World!"
Select File → Save to save your creation with an appropriate name (e.g., hello.py ).
To run your program, select Run → Run Module. You'll see the result in the interactive mode
window (Python Shell).
Congratulations! You just ran your first program in Python!
Problem
After downloading and installing Python, type import this into the Python command line and see
what happens. Then, click the "Download dataset" button below and copy the Zen of Python into the
space provided.
Problem 2
Variables and Some Arithmetic
Variables and Some Arithmetic
One of the most important features of any programming language is its ability to
manipulate variables. A variable is just a name that refers to a value;; you can
think of a variable as a box that stores a piece of data.
In Python, the basic data types are strings and numbers. There are two types of numbers: integers
(both positive and negative) and floats (fractional numbers with a decimal point). You can assign
numbers to variables very easily. Try running the following program:
a = 324
b = 24
c = a -‐ b
print 'a -‐ b is', c
In the above code, a, b, and c are all integers, and 'a - b is' is a string. The result of this program is
to print:
a -‐ b is 300
You can now use all common arithmetic operations involving numbers:
Addition: 2 + 3 == 5
Subtraction: 5 -‐ 2 == 3
Multiplication: 3 * 4 == 12
Division: 15 / 3 == 5
Division remainder: 18 % 5 == 3
Exponentiation: 2 ** 3 == 8
It is important to note that if you try to divide two integers, Python always rounds down the result
(so 18/5 == 3 ).
To obtain a precise result for this division, you need to indicate floating point division;; either of the
following expressions results in a "float" data type: 18.0/5 == 3.6 or float(18)/5 == 3.6
In Python, the single equals sign ( = ) means "assign a value to a variable". For example, a = 3
assigns 3 to the integer a. In order to denote equality, Python uses the double equals sign ( == ).
In Python, a string is an ordered sequence of letters, numbers and other characters. You can
create string variables just like you did with :
a = "Hello"
b = "World"
Notice that the string must be surrounded by " or ' (but not a mix of both). You can use quotes
inside the string, as long as you use the opposite type of quotes to surround the string, e.g., a =
"Monty Python's Flying Circus" or b = 'Project "Rosalind"' .
String operations differ slightly from operations on numbers:
a = 'Rosalind'
b = 'Franklin'
c = '!'
print a + ' ' + b + c*3
Output:
Rosalind Franklin!!!
Problem
Given: Two positive integers and , each less than 1000.

Return: The integer corresponding to the square of the hypotenuse of the right triangle whose legs
have lengths and .
Notes:
1. The dataset changes every time you click "Download dataset".

2. We check only your final answer to the downloaded dataset in the box below, not your code itself.
If you would like to provide your code as well, you may use the upload tool. Please also note that
the correct answer to this problem will not in general be 34;; it is simply an example of what you
should return in the specific case that the legs of the triangle have length 3 and 5.
Sample Dataset
3 5
Sample Output
34
Problem 3
Strings and Lists
Strings and lists
We've already seen numbers and strings, but Python also has variable types that
can hold more than one piece of data at a time. The simplest such variable is a
list.
You can assign data to a list in the following way: list_name = [item_1, item_2, ...,
item_n] . The items of the list can be of any other type: integer, float, string. You even explore your
inner Zen and make lists of lists!
Any item in a list can be accessed by its index, or the number that indicates its place in the list.
For example, try running the following code:
tea_party = ['March Hare', 'Hatter', 'Dormouse', 'Alice']
print tea_party[2]
Your output should be:
Dormouse
Note that the output was not Hatter , as you might have guessed. This is because in Python,
indexing begins with 0, not 1. This property is called 0-based numbering, and it's shared by many
programming languages.
You can easily change existing list items by reassigning them. Try running the following:
tea_party[1] = 'Cheshire Cat'

print tea_party
This code should output the list with "Hatter" replaced by "Cheshire Cat":
March Hare, Cheshire Cat, Dormouse, Alice
You can also add items to the end of an existing list by using the function append() :
tea_party.append('Jabberwocky')
print tea_party
This code outputs the following:
March Hare, Cheshire Cat, Dormouse, Alice, Jabberwocky
If you need to obtain only some of a list, you can use the notation list_name[a:b] to get only
those from index a up to but not including index b . For example, tea_party[1:3] returns
Cheshire Cat, Dormouse , not Cheshire Cat, Dormouse, Alice . This process is called "list
slicing".
If the first index of the slice is unspecified, then Python assumes that the slice begins with the
beginning of the list (i.e., index 0);; if the second index of the slice is unspecified, then you will
obtain the items at the end of the list. For example, tea_party[:2] returns March Hare,
Cheshire Cat and tea_party[3:] returns Alice, Jabberwocky .
You can also use negative indices to count items backtracking from the end of the list. So
tea_party[-‐2:] returns the same output as tea_party[3:] : Alice, Jabberwocky .
Finally, Python equips you with the magic ability to slice strings the same way that you slice lists.
A string can be considered as a list of characters, each of which having its own index starting from
0. For example, try running the following code:
a = 'flimsy'
b = 'miserable'
c = b[0:1] + a[2:]
print c
This code will output the string formed by the first character of miserable and the last four
characters of flimsy :
mimsy
Problem
Given: A string of length at most 200 letters and four integers , , and .
Return: The slice of this string from indices through and through (with space in between),
inclusively.
Sample Dataset
HumptyDumptysatonawallHumptyDumptyhadagreatfallAlltheKingshorsesandallt
heKingsmenCouldntputHumptyDumptyinhisplaceagain.
22 27 97 102
Sample Output
Humpty Dumpty
Problem 4
Conditions and Loops
Conditions and Loops
If you need Python to choose between two actions, then you can use an
if / else statement. Try running this example code:
a = 42
if a < 10:
print 'the number is less than 10'
else:
print 'the number is greater or equal to 10'
Note the indentation and punctuation (especially the colons), because they are important.
If we leave out an else , then the program continues on. Try running this program with different
initial values of a and b :
if a + b == 4:
print 'printed when a + b equals four'
print 'always printed'
If you want to repeat an action several times, you can use a while loop. The following program
prints Hello once, then adds 1 to the greetings counter. It then prints Hello twice because
greetings is equal to 2, then adds 1 to greetings . After printing Hello three times,
greetings becomes 4, and the while condition of greetings <= 3 is no longer satisfied, so
the program would continue past the while loop.
greetings = 1
while greetings <= 3:
print 'Hello! ' * greetings
greetings = greetings + 1
Be careful! If you accidentally create an infinite loop, your program will freeze and you will have to
abort it. Here's an example of an infinite loop. Make sure you see why it will never exit the while
loop:
greetings = 1
while greetings <= 3:
print 'Hello! ' * greetings
greetings = greetings + 0 # Bug here
If you want to carry out some action on every element of a list, the for loop will be handy
names = ['Alice', 'Bob', 'Charley']

for name in names:
print 'Hello, ' + name
And if you want to repeat an action exactly times, you can use the following template:
n = 10
for i in range(n):
print i
In the above code, range is a function that creates a list of integers between and , where is
not included.
Finally, try seeing what the following code prints when you run it:
print range(5, 12)
More information about loops and conditions can be found in the Python documentation.
Problem
Given: Two positive integers and ( ).
Return: The sum of all odd integers from through , inclusively.
Sample Dataset
100 200
Sample Output
7500
Hint
You can use a % 2 == 1 to test if a is odd.
Problem 5
Working with Files
Reading and Writing
In Rosalind, sample datasets are given as files. Python has a lot of functions for
reading and writing information in files.
To access a file, you must first open it. To do so, you can use the open()
function, which takes two parameters: the name of the target file and the mode. Three modes are
available:
r - read mode (the file is opened for reading)

w - write mode (the file is opened for writing, and if a file having the same name exists, it will
be erased)
a - append mode (the file is opened for appending, which means that data is only to be added
to the existing data in the file)
f = open('input.txt', 'r')
This code told Python to open the file input.txt in r mode and store the result of this operation
in a file object called f .
To obtain data from the file object you created, you can apply the following methods:
The command f.read(n) returns bytes of data from the file as a string. When the size
parameter is omitted, the entire contents of the file will be read and returned.
The command f.readline() takes a single line from the file. Every line (except the last line of
file) terminates in a newline character ( \n ). To remove this character from the end of a line you
have read, use the .strip() method. Note that every time you call .readline() it takes the
next line in the file.
The command f.readlines() returns a list containing every line in the file. If you need to obtain a
particular line, you can use a list item index, e.g., f.readlines()[2] returns the third line of the
file object f (don't forget that Python utilizes 0-based numbering!)
An alternative way to read lines is to loop over the file object.
for line in f:

print line
Using this loop, you can do anything you need with every line in the file.
If the data in the file are not separated by new lines but rather by whitespace, commas, or any
other delimeter, then all three commands above will return the data only in the form of lines. As a
workaround, you can use the command line.split() . It uses whitespace in addition to \n as
delimeters by default, and runs of the same delimiter are regarded as a single separating space.
For example,
'Beautiful is better than ugly.\n'.split() returns ['Beautiful', 'is', 'better',

'than', 'ugly.']
You can even specify the delimiter as a parameter of line.split() :
'Explicit, is better, than implicit.'.split(",") returns ['Explicit', ' is

better', ' than implicit.']
Another convenient command for file parsing is .splitlines() . It returns a list of the lines in the
string, breaking at line boundaries. Line breaks are not included.
'Simple is\nbetter than\ncomplex.\n'.splitlines() returns ['Simple is', 'better

than', 'complex.']
When you at last complete all your calculations and obtain a result, you need to store it
somewhere. To save a file, output the desired file in write mode (if there is no such file, it will be
created automatically):
f = open('output.txt', 'w')
You can then write your data using .write() method.
f.write('Any data you want to write into file')
The command f.write(string) writes the contents of string to file f . If you want to write
something other than a string (an integer say), you must first convert it to a string by using the
function str() .
inscription = ['Rosalind Elsie Franklin ', 1920, 1958]

s = str(inscription)
f.write(s)
You also can write list items into a file one at a time by using a for loop:
for i in inscription:

output.write(str(i) + '\n')
Adding \n to str(i) means that every item will start with a new line.
When you are finished writing file, don't forget that you must close it using the command
f.close() . It's a good habit to get into.
Problem
Given: A file containing at most 1000 lines.

Return: A file containing all the even-numbered lines from the original file. Assume 1-based
numbering of lines.
Sample Dataset
`Bravely bold Sir Robin rode forth from Camelot

Yes, brave Sir Robin turned about
He was not afraid to die, O brave Sir Robin
And gallantly he chickened out
He was not at all afraid to be killed in nasty ways
Bravely talking to his feet
Brave, brave, brave, brave Sir Robin
He beat a very brave retreat
Sample Output
Yes, brave Sir Robin turned about

And gallantly he chickened out
Bravely talking to his feet
He beat a very brave retreat
Problem 6
Dictionaries
Intro to Python dictionary
We've already used lists and strings to store and process bunch of data. Python
also has a variable type to matching one items (i.e. keys) to others (i.e. values)
called dictionary. Dictionary is similar to list but instead of automatic index you
provide your own index called key. You can assign data to a dictionary as follows:
phones = {'Zoe':'232-‐43-‐58', 'Alice':'165-‐88-‐56'} . As with lists for a value could be
used any type: string, number, float even dict or list. For keys you can use only strings, numbers,
floats and other immutable types. Accessing values also similar to lists:
phones = {'Zoe':'232-‐43-‐58', 'Alice':'165-‐88-‐56'}

print phones['Zoe']
Output should be:
232-‐43-‐58
Adding new value to dictionary or assigning an existent can be done the same way as you do it
with variable
phones['Zoe'] = '658-‐99-‐55'
phones['Bill'] = '342-‐18-‐25'
print phones
You should see the following:
{'Bill': '342-‐18-‐25', 'Zoe': '658-‐99-‐55', 'Alice': '165-‐88-‐56'}
Note that new 'Bill' appeared in the beginning not in the end as you might expected. The thing
is that dictionary basically does not have any ordering. New value appear in random place.
Remember that the dictionary is case-sensitive if you are using strings as keys. Keep in mind that
'key' and 'Key' are different keys:
d = {}
d['key'] = 1
d['Key'] = 2
d['KEY'] = 3
print d
Output:
{'KEY': 3, 'Key': 2, 'key': 1}
Note how we created an empty dictionary with d = {} . This could be useful in case you need to
add values to dictionary dynamically (for example, when reading a file). If you need to check is
there a key in dictionary you can use key in d syntax:
if 'Peter' in phones:

print "We know Peter's phone"
else:
print "We don't know Peter's phone"
Output:
We don't know Peter's phone
In case you need to delete a value from a dictionary please use del :
phones = {'Zoe':'232-‐43-‐58', 'Alice':'165-‐88-‐56'}

del phones['Zoe']
print phones
Output:
{'Alice': '165-‐88-‐56'}
Problem
Given: A string of length at most 10000 letters.

Return: How many times any word occurred in string. Each letter case (upper or lower) in word
matters. Lines in output can be in any order.
Sample Dataset
We tried list and we tried dicts also we tried Zen
Sample Output
and 1
We 1
tried 3
dicts 1
list 1
we 2
also 1
Zen 1
Hints
To iterate over words in string you can split it by space:
for word in str.split(' '):

print word
To have nice output of dictionary you can use .items() method:
for key, value in dict.items():

print key
print value
Problem 7
Counting DNA Nucleotides
A Rapid Introduction to Molecular Biology
Making up all living material, the cell is

considered to be the building block of life.
The nucleus, a component of most
eukaryotic cells, was identified as the
hub of cellular activity 150 years ago. Viewed under a light
microscope, the nucleus appears only as a darker region
of the cell, but as we increase magnification, we find that
the nucleus is densely filled with a stew of
macromolecules called chromatin. During mitosis
Figure 1. A 1900 drawing by
(eukaryotic cell division), most of the chromatin condenses Edmund Wilson of onion cells at
into long, thin strings called chromosomes. See Figure 1 different stages of mitosis. The
sample has been dyed, causing
for a figure of cells in different stages of mitosis. chromatin in the cells (which soaks
up the dye) to appear in greater
One class of the macromolecules contained in chromatin contrast to the rest of the cell.
are called nucleic acids. Early 20th century research into
the chemical identity of nucleic acids culminated with the
conclusion that nucleic acids are polymers, or repeating
chains of smaller, similarly structured molecules known as
monomers. Because of their tendency to be long and thin,
nucleic acid polymers are commonly called strands.
The nucleic acid monomer is called a nucleotide and is

used as a unit of strand length (abbreviated to nt). Each
nucleotide is formed of three parts: a sugar molecule, a
negatively charged ion called a phosphate, and a
compound called a nucleobase ("base" for short).
Polymerization is achieved as the sugar of one nucleotide
bonds to the phosphate of the next nucleotide in the chain, Figure 2. A sketch of DNA's primary
which forms a sugar-phosphate backbone for the nucleic structure.
acid strand. A key point is that the nucleotides of a
specific type of nucleic acid always contain the same sugar and phosphate molecules, and they
differ only in their choice of base. Thus, one strand of a nucleic acid can be differentiated from
another based solely on the order of its bases;; this ordering of bases defines a nucleic acid's
primary structure.
For example, Figure 2 shows a strand of deoxyribose nucleic acid (DNA), in which the sugar is
called deoxyribose, and the only four choices for nucleobases are molecules called adenine (A),
cytosine (C), guanine (G), and thymine (T).
For reasons we will soon see, DNA is found in all living organisms on Earth, including bacteria;; it is
even found in many viruses (which are often considered to be nonliving). Because of its importance,
we reserve the term genome to refer to the sum total of the DNA contained in an organism's
chromosomes.
Problem
A string is simply an ordered collection of symbols selected from some alphabet and formed into a
word;; the length of a string is the number of symbols that it contains.
An example of a length 21 DNA string (whose alphabet contains the symbols 'A', 'C', 'G', and 'T') is
"ATGCTTCAGAAAGGTCTTACG."
Given: A DNA string of length at most 1000 nt.

Return: Four integers (separated by spaces) counting the respective number of times that the
symbols 'A', 'C', 'G', and 'T' occur in .
Sample Dataset
AGCTTTTCATTCTGACTGCAACGGGCAATATGTCTCTGTGTGGATTAAAAAAAGAGTGTCTGATAGCAGC
Sample Output
20 12 17 21

Problem 8
Transcribing DNA into RNA
The Second Nucleic Acid
In “Counting DNA Nucleotides”, we

described the primary structure of a
nucleic acid as a polymer of nucleotide
units, and we mentioned that the
omnipresent nucleic acid DNA is composed of a varied
sequence of four bases.
Yet a second nucleic acid exists alongside DNA in the

chromatin;; this molecule, which possesses a different
sugar called ribose, came to be known as ribose nucleic
acid, or RNA. RNA differs further from DNA in that it
contains a base called uracil in place of thymine;;
structural differences between DNA and RNA are shown in Figure 1. Structural differences
Figure 1. Biologists initially believed that RNA was only between RNA and DNA
contained in plant cells, whereas DNA was restricted to
animal cells. However, this hypothesis dissipated as improved chemical methods discovered both
nucleic acids in the cells of all life forms on Earth.
The primary structure of DNA and RNA is so similar because the former serves as a blueprint for
the creation of a special kind of RNA molecule called messenger RNA, or mRNA. mRNA is
created during RNA transcription, during which a strand of DNA is used as a template for
constructing a strand of RNA by copying nucleotides one at a time, where uracil is used in place of
thymine.
In eukaryotes, DNA remains in the nucleus, while RNA can enter the far reaches of the cell to carry
out DNA's instructions. In future problems, we will examine the process and ramifications of RNA
transcription in more detail.
Problem
An RNA string is a string formed from the alphabet containing 'A', 'C', 'G', and 'U'.
Given a DNA string corresponding to a coding strand, its transcribed RNA string is formed by
replacing all occurrences of 'T' in with 'U' in .
Given: A DNA string having length at most 1000 nt.

Return: The transcribed RNA string of .
Sample Dataset
GATGGAACTTGACTACGTAAATT
Sample Output
GAUGGAACUUGACUACGUAAAUU
Problem 9
Complementing a Strand of DNA
The Secondary and Tertiary Structures of DNA
In “Counting DNA Nucleotides”, we

introduced nucleic acids, and we saw
that the primary structure of a nucleic
acid is determined by the ordering of its
nucleobases along the sugar-phosphate backbone that
constitutes the bonds of the nucleic acid polymer. Yet
primary structure tells us nothing about the larger, 3-
dimensional shape of the molecule, which is vital for a
complete understanding of nucleic acids.
The search for a complete chemical structure of nucleic

acids was central to molecular biology research in the mid-
20th Century, culminating in 1953 with a publication in Figure 1. Base pairing across the
Nature of fewer than 800 words by James Watson and two strands of DNA.
Francis Crick. Consolidating a high resolution X-ray image
created by Rosalind Franklin and Raymond Gosling with a
number of established chemical results, Watson and Crick
proposed the following structure for DNA:
1. The DNA molecule is made up of two strands, running
in opposite directions.
2. Each base bonds to a base in the opposite strand.
Adenine always bonds with thymine, and cytosine
always bonds with guanine;; the complement of a
base is the base to which it always bonds;; see Figure
1.
3. The two strands are twisted together into a long spiral
staircase structure called a double helix;; see Figure Figure 2. The double helix of DNA on
the molecular scale.
2.
Because they dictate how bases from different strands interact with each other, (1) and (2) above
compose the secondary structure of DNA. (3) describes the 3-dimensional shape of the DNA
molecule, or its tertiary structure.
In light of Watson and Crick's model, the bonding of two complementary bases is called a base
pair (bp). Therefore, the length of a DNA molecule will commonly be given in bp instead of nt. By
complementarity, once we know the order of bases on one strand, we can immediately deduce the
sequence of bases in the complementary strand. These bases will run in the opposite order to
match the fact that the two strands of DNA run in opposite directions.
Problem
In DNA strings, symbols 'A' and 'T' are complements of each other, as are 'C' and 'G'.
The reverse complement of a DNA string is the string formed by reversing the symbols of ,
then taking the complement of each symbol (e.g., the reverse complement of "GTCA" is "TGAC").
Given: A DNA string of length at most 1000 bp.

Return: The reverse complement of .
Sample Dataset
AAAACCCGGT
Sample Output
ACCGGGTTTT
Problem 10
Rabbits and Recurrence Relations
Wascally Wabbits
In 1202, Leonardo of Pisa (commonly

known as Fibonacci) considered a
mathematical exercise regarding the
reproduction of a population of rabbits. He
made the following simplifying assumptions about the
population:
1. The population begins in the first month with a pair of
newborn rabbits.
2. Rabbits reach reproductive age after one month.
3. In any given month, every rabbit of reproductive age
mates with another rabbit of reproductive age. Figure 1. The growth of Fibonacci's
rabbit population for the first six
4. Exactly one month after two rabbits mate, they months.
produce one male and one female rabbit.
5. Rabbits never die or stop reproducing.
Fibonacci's exercise was to calculate how many pairs of rabbits would remain in one year. We can
see that in the second month, the first pair of rabbits reach reproductive age and mate. In the third
month, another pair of rabbits is born, and we have two rabbit pairs;; our first pair of rabbits mates
again. In the fourth month, another pair of rabbits is born to the original pair, while the second pair
reach maturity and mate (with three total pairs). The dynamics of the rabbit population are
illustrated in Figure 1. After a year, the rabbit population boasts 144 pairs.
Although Fibonacci's assumption of the rabbits' immortality
may seem a bit farfetched, his model was not unrealistic
for reproduction in a predator-free environment: European
rabbits were introduced to Australia in the mid 19th
Century, a place with no real indigenous predators for
them. Within 50 years, the rabbits had already eradicated
many plant species across the continent, leading to
irreversible changes in the Australian ecosystem and
turning much of its grasslands into eroded, practically
uninhabitable parts of the modern Outback (see Figure 2).
In this problem, we will use the simple idea of counting
rabbits to introduce a new computational topic, which
involves building up large solutions from smaller ones. Figure 2. Erosion at Lake Mungo in
New South Wales, which was
initiated by European rabbits in the
19th Century. Courtesy Pierre
Problem Pouliquin.
A sequence is an ordered collection of objects (usually numbers), which are allowed to repeat.
Sequences can be finite or infinite. Two examples are the finite sequence and the
infinite sequence of odd numbers . We use the notation to represent the -th
term of a sequence.
A recurrence relation is a way of defining the terms of a sequence with respect to the values of
previous terms. In the case of Fibonacci's rabbits from the introduction, any given month will contain
the rabbits that were alive the previous month, plus any new offspring. A key observation is that the
number of offspring in any month is equal to the number of rabbits that were alive two months prior. As
a result, if represents the number of rabbit pairs alive after the -th month, then we obtain the
Fibonacci sequence having terms that are defined by the recurrence relation
(with to initiate the sequence). Although the sequence bears
Fibonacci's name, it was known to Indian mathematicians over two millennia ago.
When finding the -th term of a sequence defined by a recurrence relation, we can simply use the
recurrence relation to generate terms for progressively larger values of . This problem introduces us
to the computational technique of dynamic programming, which successively builds up solutions by
using the answers to smaller cases.
Given: Positive integers and .
Return: The total number of rabbit pairs that will be present after months if we begin with 1 pair
and in each generation, every pair of reproduction-age rabbits produces a litter of rabbit pairs (instead
of only 1 pair).
Sample Dataset
5 3
Sample Output
19
Problem 11
Computing GC Content
Identifying Unknown DNA Quickly
A quick method used by early computer

software to determine the language of a
given piece of text was to analyze the
frequency with which each letter
appeared in the text. This strategy was used because
each language tends to exhibit its own letter frequencies,
and as long as the text under consideration is long
enough, software will correctly recognize the language
quickly and with a very low error rate. See Figure 1 for a
table compiling English letter frequencies.
Figure 1. The table above was
You may ask: what in the world does this linguistic computed from a large number of
English words and shows for any
problem have to do with biology? Although two members of letter the frequency with which it
the same species will have different genomes, they still appears in those words. These
share the vast percentage of their DNA;; notably, 99.9% of frequencies can be used to reliably
identify a piece of English text and
the 3.2 billion base pairs in a human genome are common differentiate it from that of another
to almost all humans (i.e., excluding people having major language. Taken from
http://en.wikipedia.org/wiki/File:English_letter_freque
genetic defects). For this reason, biologists will speak of
the human genome, meaning an average-case genome
derived from a collection of individuals. Such an average case genome can be assembled for any
species, a challenge that we will soon discuss.
The biological analog of identifying unknown text arises when researchers encounter a molecule of
DNA deriving from an unknown species. Because of the base pairing relations of the two DNA
strands, cytosine and guanine will always appear in equal amounts in a double-stranded DNA
molecule. Thus, to analyze the symbol frequencies of DNA for comparison against a database, we
compute the molecule's GC-content, or the percentage of its bases that are either cytosine or
guanine.
In practice, the GC-content of most eukaryotic genomes hovers around 50%. However, because
genomes are so long, we may be able to distinguish species based on very small discrepancies in
GC-content;; furthermore, most prokaryotes have a GC-content significantly higher than 50%, so
that GC-content can be used to quickly differentiate many prokaryotes and eukaryotes by using
relatively small DNA samples.
Problem
The GC-content of a DNA string is given by the percentage of symbols in the string that are 'C' or 'G'.
For example, the GC-content of "AGCTATAG" is 37.5%. Note that the reverse complement of any
DNA string has the same GC-content.
DNA strings must be labeled when they are consolidated into a database. A commonly used method
of string labeling is called FASTA format. In this format, the string is introduced by a line that begins
with '>', followed by some labeling information. Subsequent lines contain the string itself;; the first line
to begin with '>' indicates the label of the next string.
In Rosalind's implementation, a string in FASTA format will be labeled by the ID "Rosalind_xxxx",
where "xxxx" denotes a four-digit code between 0000 and 9999.
Given: At most 10 DNA strings in FASTA format (of length at most 1 kbp each).
Return: The ID of the string having the highest GC-content, followed by the GC-content of that
string. Rosalind allows for a default error of 0.001 in all decimal answers unless otherwise stated;;
please see the note on absolute error below.
Sample Dataset
>Rosalind_6404
CCTGCGGAAGATCGGCACTAGAATAGCCAGAACCGTTTCTCTGAGGCTTCCGGCCTTCCC
TCCCACTAATAATTCTGAGG
>Rosalind_5959
CCATCGGTAGCGCATCCTTAGTCCAATTAAGTCCCTATCCAGGCGCTCCGCCGAAGGTCT
ATATCCATTTGTCAGCAGACACGC
>Rosalind_0808
CCACCCTCGTGGTATGGCTAGGCATTCAGGAACCGGAGAACGCTTCAGACCAGCCCGGAC
TGGGAACCTGCGGGCAGTAGGTGGAAT
Sample Output
Rosalind_0808
60.919540
Note on Absolute Error
We say that a number is within an absolute error of to a correct solution if is within of the
correct solution. For example, if an exact solution is 6.157892, then for to be within an absolute
error of 0.001, we must have that , or .
Error bounding is a vital practical tool because of the inherent round-off error in representing
decimals in a computer, where only a finite number of decimal places are allotted to any number.
After being compounded over a number of operations, this round-off error can become evident. As a
result, rather than testing whether two numbers are equal with , you may wish to simply
verify that is very small.
The mathematical field of numerical analysis is devoted to rigorously studying the nature of
computational approximation.
Problem 12
Counting Point Mutations
Evolution as a Sequence of Mistakes

A mutation is simply a mistake that
occurs during the creation or copying of a
nucleic acid, in particular DNA. Because
nucleic acids are vital to cellular
functions, mutations tend to cause a
ripple effect throughout the cell. Although
mutations are technically mistakes, a
very rare mutation may equip the cell with a beneficial
attribute. In fact, the macro effects of evolution are
attributable by the accumulated result of beneficial
microscopic mutations over many generations.
The simplest and most common type of nucleic acid

mutation is a point mutation, which replaces one base Figure 1. A point mutation in DNA
changing a C-G pair to an A-T pair.
with another at a single nucleotide. In the case of DNA, a
point mutation must change the complementary base
accordingly;; see Figure 1.
Two DNA strands taken from different organism or species genomes are homologous if they share
a recent ancestor;; thus, counting the number of bases at which homologous strands differ provides
us with the minimum number of point mutations that could have occurred on the evolutionary path
between the two strands.
We are interested in minimizing the number of (point) mutations separating two species because of
the biological principle of parsimony, which demands that evolutionary histories should be as
simply explained as possible.
Problem
Given two strings and of equal length, the Hamming

distance between and , denoted , is the number
of corresponding symbols that differ in and . See Figure 2.
Figure 2. The Hamming distance
Given: Two DNA strings and of equal length (not between these two strings is 7.
Mismatched symbols are colored
exceeding 1 kbp). red.
Return: The Hamming distance .
Sample Dataset
GAGCCTACTAACGGGAT
CATCGTAATGACGGCCT
Sample Output
Problem 13
Mendel's First Law
Introduction to Mendelian Inheritance
Modern laws of inheritance were first

described by Gregor Mendel (an
Augustinian Friar) in 1865. The
contemporary hereditary model, called
blending inheritance, stated that an organism must
exhibit a blend of its parent's traits. This rule is obviously
violated both empirically (consider the huge number of
people who are taller than both their parents) and
statistically (over time, blended traits would simply blend
into the average, severely limiting variation).
Mendel, working with thousands of pea plants, believed

that rather than viewing traits as continuous processes, Figure 1. A Punnett square
they should instead be divided into discrete building blocks representing the possible outcomes
called factors. Furthermore, he proposed that every factor of crossing a heterozygous
organism (Yy) with a homozygous
possesses distinct forms, called alleles. recessive organism (yy);; here, the
dominant allele Y corresponds to
In what has come to be known as his first law (also yellow pea pods, and the recessive
known as the law of segregation), Mendel stated that every allele y corresponds to green pea
pods.
organism possesses a pair of alleles for a given factor. If an
individual's two alleles for a given factor are the same, then
it is homozygous for the factor;; if the alleles differ, then the individual is heterozygous. The first
law concludes that for any factor, an organism randomly passes one of its two alleles to each
offspring, so that an individual receives one allele from each parent.
Mendel also believed that any factor corresponds to only two possible alleles, the dominant and
recessive alleles. An organism only needs to possess one copy of the dominant allele to display
the trait represented by the dominant allele. In other words, the only way that an organism can
display a trait encoded by a recessive allele is if the individual is homozygous recessive for that
factor.
We may encode the dominant allele of a factor by a capital letter (e.g., ) and the recessive allele
by a lower case letter (e.g., ). Because a heterozygous organism can possess a recessive allele
without displaying the recessive form of the trait, we henceforth define an organism's genotype to
be its precise genetic makeup and its phenotype as the physical manifestation of its underlying
traits.
The different possibilities describing an individual's inheritance of two alleles from its parents can be
represented by a Punnett square;; see Figure 1 for an example.
Problem
Probability is the mathematical study of randomly occurring

phenomena. We will model such a phenomenon with a
random variable, which is simply a variable that can take a
number of different distinct outcomes depending on the result
of an underlying random process.
For example, say that we have a bag containing 3 red balls
and 2 blue balls. If we let represent the random variable Figure 2. The probability of any
outcome (leaf) in a probability tree
corresponding to the color of a drawn ball, then the diagram is given by the product of
probability of each of the two outcomes is given by probabilities from the start of the tree
and . to the outcome. For example, the
probability that X is blue and Y is
blue is equal to (2/5)(1/4), or 1/10.
Random variables can be combined to yield new random
variables. Returning to the ball example, let model the color
of a second ball drawn from the bag (without replacing the first ball). The probability of being red
depends on whether the first ball was red or blue. To represent all outcomes of and , we therefore
use a probability tree diagram. This branching diagram represents all possible individual
probabilities for and , with outcomes at the endpoints ("leaves") of the tree. The probability of any
outcome is given by the product of probabilities along the path from the beginning of the tree;; see
Figure 2 for an illustrative example.
An event is simply a collection of outcomes. Because outcomes are distinct, the probability of an
event can be written as the sum of the probabilities of its constituent outcomes. For our colored ball
example, let be the event " is blue." is equal to the sum of the probabilities of two different
outcomes: , or
(see Figure 2 above).
Given: Three positive integers , , and , representing a population containing

organisms: individuals are homozygous dominant for a factor, are heterozygous, and are
homozygous recessive.
Return: The probability that two randomly selected mating organisms will produce an individual
possessing a dominant allele (and thus displaying the dominant phenotype). Assume that any two
organisms can mate.
Sample Dataset
2 2 2
Sample Output
0.78333
Hint
Consider simulating inheritance on a number of small test cases in order to check your solution.
Problem 14
Translating RNA into Protein
The Genetic Code

Just as nucleic acids are polymers of
nucleotides, proteins are chains of
smaller molecules called amino acids;;
20 amino acids commonly appear in
every species. Just as the primary
structure of a nucleic acid is given by the
order of its nucleotides, the primary
structure of a protein is the order of its amino acids. Some
proteins are composed of several subchains called
polypeptides, while others are formed of a single
polypeptide;; see Figure 1.
Proteins power every practical function carried out by the Figure 1. The human hemoglobin
cell, and so presumably, the key to understanding life lies molecule consists of 4 polypeptide
in interpreting the relationship between a chain of amino chains;; α subunits are shown in red
and β subunits are shown in blue
acids and the function of the protein that this chain of
amino acids eventually constructs. Proteomics is the field
devoted to the study of proteins.
How are proteins created? The genetic code, discovered throughout the course of a number of
ingenious experiments in the late 1950s, details the translation of an RNA molecule called
messenger RNA (mRNA) into amino acids for protein creation. The apparent difficulty in translation
is that somehow 4 RNA bases must be translated into a language of 20 amino acids;; in order for
every possible amino acid to be created, we must translate 3-nucleobase strings (called codons)
into amino acids. Note that there are possible codons, so that multiple codons may
encode the same amino acid. Two special types of codons are the start codon (AUG), which
codes for the amino acid methionine always indicates the start of translation, and the three stop
codons (UAA, UAG, UGA), which do not code for an amino acid and cause translation to end.
The notion that protein is always created from RNA, which in turn is always created from DNA,
forms the central dogma of molecular biology. Like all dogmas, it does not always hold;;
however, it offers an excellent approximation of the truth.
A eukaryotic organelle called a ribosome creates peptides by using a helper molecule called
transfer RNA (tRNA). A single tRNA molecule possesses a string of three RNA nucleotides on one
end (called an anticodon) and an amino acid at the other end. The ribosome takes an RNA
molecule transcribed from DNA (see “Transcribing DNA into RNA”), called messenger RNA
(mRNA), and examines it one codon at a time. At each step, the tRNA possessing the
complementary anticodon bonds to the mRNA at this location, and the amino acid found on the
opposite end of the tRNA is added to the growing peptide chain before the remaining part of the
tRNA is ejected into the cell, and the ribosome looks for the next tRNA molecule.
Not every RNA base eventually becomes translated into a protein, and so an interval of RNA (or an
interval of DNA translated into RNA) that does code for a protein is of great biological interest;; such
an interval of DNA or RNA is called a gene. Because protein creation drives cellular processes,
genes differentiate organisms and serve as a basis for heredity, or the process by which traits are
inherited.
Problem
The 20 commonly occurring amino acids are abbreviated by using 20 letters from the English alphabet
(all letters except for B, J, O, U, X, and Z). Protein strings are constructed from these 20 symbols.
Henceforth, the term genetic string will incorporate protein strings along with DNA strings and RNA
strings.
The RNA codon table dictates the details regarding the encoding of specific codons into the amino
acid alphabet.
Given: An RNA string corresponding to a strand of mRNA (of length at most 10 kbp).
Return: The protein string encoded by .
Sample Dataset
AUGGCCAUGGCGCCCAGAACUGAGAUCAAUAGUACCCGUAUUAACGGGUGA
Sample Output
MAMAPRTEINSTRING
Problem 15
Finding a Motif in DNA
Combing Through the Haystack
Finding the same interval of DNA in the

genomes of two different organisms (often
taken from different species) is highly
suggestive that the interval has the same
function in both organisms. Figure 1. The human chromosomes
stained with a probe for Alu
elements, shown in green.
We define a motif as such a commonly shared interval of
DNA. A common task in molecular biology is to search an
organism's genome for a known motif.
The situation is complicated by the fact that genomes are riddled with intervals of DNA that occur
multiple times (possibly with slight modifications), called repeats. These repeats occur far more
often than would be dictated by random chance, indicating that genomes are anything but random
and in fact illustrate that the language of DNA must be very powerful (compare with the frequent
reuse of common words in any human language).
The most common repeat in humans is the Alu repeat, which is approximately 300 bp long and
recurs around a million times throughout every human genome (see Figure 1). However, Alu has
not been found to serve a positive purpose, and appears in fact to be parasitic: when a new Alu
repeat is inserted into a genome, it frequently causes genetic disorders.
Problem
Given two strings and , is a substring of if is contained as a contiguous collection of symbols
in (as a result, must be no longer than ).
The position of a symbol in a string is the total number of symbols found to its left, including itself
(e.g., the positions of all occurrences of 'U' in "AUGCUUCAGAAAGGUCUUACG" are 2, 5, 6, 15, 17,
and 18). The symbol at position of is denoted by .
A substring of can be represented as , where and represent the starting and ending
positions of the substring in ;; for example, if = "AUGCUUCAGAAAGGUCUUACG", then =
"UGCU".
The location of a substring is its beginning position ;; note that will have multiple locations
in if it occurs more than once as a substring of (see the Sample below).
Given: Two DNA strings and (each of length at most 1 kbp).
Return: All locations of as a substring of .
Sample Dataset
GATATATGCATATACTT
ATAT
Sample Output
2 4 10
Note
Different programming languages use different notations for positions of symbols in strings. Above,
we use 1-based numbering, as opposed to 0-based numbering, which is used in Python. For
= "AUGCUUCAGAAAGGUCUUACG", 1-based numbering would state that = 'A' is the first
symbol of the string, whereas this symbol is represented by in 0-based numbering. The idea of
0-based numbering propagates to substring indexing, so that becomes "GCUU" instead of
"UGCU".
Note that in some programming languages, such as Python, s[j:k] returns only fragment from index
up to but not including index , so that s[2:5] actually becomes "UGC", not "UGCU".
Problem 16
Consensus and Profile
Finding a Most Likely Common Ancestor
In “Counting Point Mutations”, we calculated the minimum number of symbol
mismatches between two strings of equal length to model the problem of finding
the minimum number of point mutations occurring on the evolutionary path
between two homologous strands of DNA. If we instead have several homologous
strands that we wish to analyze simultaneously, then the natural problem is to find an average-case
strand to represent the most likely common ancestor of the given strands.
Problem
A matrix is a rectangular table of values divided into rows and columns. An matrix has
rows and columns. Given a matrix , we write to indicate the value found at the intersection of
row and column .
Say that we have a collection of DNA strings, all having the same length . Their profile matrix is a
matrix in which represents the number of times that 'A' occurs in the th position of
one of the strings, represents the number of times that C occurs in the th position, and so on
(see below).
A consensus string is a string of length formed from our collection by taking the most common
symbol at each position;; the th symbol of therefore corresponds to the symbol having the maximum
value in the -th column of the profile matrix. Of course, there may be more than one most common
symbol, leading to multiple possible consensus strings.
A T C C A G C T
G G G C A A C T
A T G G A T C T
DNA Strings A A G C A A C C
T T G G A A C T
A T G C C A T T
A T G G C A C T
A 5 1 0 0 5 5 0 0
Profile C 0 0 1 4 2 0 6 1
G 1 1 6 3 0 1 0 0
T 1 5 0 0 0 1 1 6
Consensus A T G C A A C T
Given: A collection of at most 10 DNA strings of equal length (at most 1 kbp) in FASTA format.
Return: A consensus string and profile matrix for the collection. (If several possible consensus
strings exist, then you may return any one of them.)
Sample Dataset
>Rosalind_1
ATCCAGCT
>Rosalind_2
GGGCAACT
>Rosalind_3
ATGGATCT
>Rosalind_4
AAGCAACC
>Rosalind_5
TTGGAACT
>Rosalind_6
ATGCCATT
>Rosalind_7
ATGGCACT
Sample Output
ATGCAACT
A: 5 1 0 0 5 5 0 0
C: 0 0 1 4 2 0 6 1
G: 1 1 6 3 0 1 0 0
T: 1 5 0 0 0 1 1 6
Problem 17
Mortal Fibonacci Rabbits
Wabbit Season
In “Rabbits and Recurrence Relations”,

we mentioned the disaster caused by
introducing European rabbits into
Australia. By the turn of the 20th Century,
the situation was so out of control that the creatures could
not be killed fast enough to slow their spread (see Figure
1).
The conclusion? Build a fence! The fence, intended to Figure 1. A c.1905 photo from
preserve the sanctity of Western Australia, was completed Australia of a cart loaded to the hilt
with rabbit skins.
in 1907 after undergoing revisions to push it back as the
bunnies pushed their frontier ever westward (see Figure 2).
If it sounds like a crazy plan, the Australians at the time
seem to have concurred, as shown by the cartoon in
Figure 3.
By 1950, Australian rabbits numbered 600 million, causing

the government to decide to release a virus (called
myxoma) into the wild, which cut down the rabbits until
they acquired resistance. In a final Hollywood twist,
another experimental rabbit virus escaped in 1991, and
some resistance has already been observed. Figure 2. Western Australia's rabbit
fence is actually not the longest
The bunnies will not be stopped, but they don't live forever, fence in the world as the sign
claims. That honor goes to a 3,500
and so in this problem, our aim is to expand Fibonacci's mile fence in southeastern Australia
rabbit population model to allow for mortal rabbits. built to keep out dingoes. Courtesy
Matt Pounsett.
Problem
Recall the definition of the Fibonacci numbers from “Rabbits and Recurrence Relations”, which followed
the recurrence relation and assumed that each pair of rabbits reaches maturity
in one month and produces a single pair of offspring (one
male, one female) each subsequent month.
Our aim is to somehow modify this recurrence relation to
achieve a dynamic programming solution in the case that all
rabbits die out after a fixed number of months. See Figure 4
for a depiction of a rabbit tree in which rabbits live for three
months (meaning that they reproduce only twice before dying).
Given: Positive integers and . Figure 3. An 1884 cartoon from the
Queensland Figaro proposing how
Return: The total number of pairs of rabbits that will remain the rabbits viewed their fence.
after the -th month if all rabbits live for months.
Sample Dataset
6 3
Sample Output
4
Figure 4. A figure illustrating the
propagation of Fibonacci's rabbits if
they die after three months.
Problem 18
Overlap Graphs
A Brief Introduction to Graph Theory
Networks arise everywhere in the practical world, especially in biology. Networks
are prevalent in popular applications such as modeling the spread of disease, but
the extent of network applications spreads far beyond popular science. Our first
question asks how to computationally model a network without actually needing
to render a picture of the network.
First, some terminology: graph is the technical term for a network;; a graph is made up of hubs
called nodes (or vertices), pairs of which are connected via segments/curves called edges. If an
edge connects nodes and , then it is denoted by (or equivalently ).
an edge is incident to nodes and ;; we say that and are adjacent to each other;;
the degree of is the number of edges incident to it;;
a walk is an ordered collection of edges for which the ending node of one edge is the starting
node of the next (e.g., , , , etc.);;
a path is a walk in which every node appears in at most two edges;;
path length is the number of edges in the path;;
a cycle is a path whose final node is equal to its first node (so that every node is incident to
exactly two edges in the cycle);; and
the distance between two vertices is the length of the shortest path connecting them.
Graph theory is the abstract mathematical study of graphs and their properties.
Problem
A graph whose nodes have all been labeled can be represented by an adjacency list, in which each
row of the list contains the two node labels corresponding to a unique edge.
A directed graph (or digraph) is a graph containing directed edges, each of which has an
orientation. That is, a directed edge is represented by an arrow instead of a line segment;; the starting
and ending nodes of an edge form its tail and head, respectively. The directed edge with tail and
head is represented by (but not by ). A directed loop is a directed edge of the form
.
For a collection of strings and a positive integer , the overlap graph for the strings is a directed
graph in which each string is represented by a node, and string is connected to string with a
directed edge when there is a length suffix of that matches a length prefix of , as long as
;; we demand to prevent directed loops in the overlap graph (although directed cycles may
be present).
Given: A collection of DNA strings in FASTA format having total length at most 10 kbp.
Return: The adjacency list corresponding to . You may return edges in any order.
Sample Dataset
>Rosalind_0498
AAATAAA
>Rosalind_2391
AAATTTT
>Rosalind_2323
TTTTCCC
>Rosalind_0442
AAATCCC
>Rosalind_5013
GGGTGGG
Sample Output
Rosalind_0498 Rosalind_2391
Note on Visualizing Graphs
If you are looking for a way to actually visualize graphs as you are working through the Rosalind
site, then you may like to consider Graphviz (link here), a cross-platform application for rendering
graphs.
Problem 19
Calculating Expected Offspring
The Need for Averages
Averages arise everywhere. In sports, we want to project the average number of
games that a team is expected to win;; in gambling, we want to project the
average losses incurred playing blackjack;; in business, companies want to
calculate their average expected sales for the next quarter.
Molecular biology is not immune from the need for averages. Researchers need to predict the
expected number of antibiotic-resistant pathogenic bacteria in a future outbreak, estimate the
predicted number of locations in the genome that will match a given motif, and study the
distribution of alleles throughout an evolving population. In this problem, we will begin discussing
the third issue;; first, we need to have a better understanding of what it means to average a random
process.
Problem
For a random variable taking integer values between 1 and , the expected value of is
. The expected value offers us a way of taking the long-term average
of a random variable over a large number of trials.
As a motivating example, let be the number on a six-sided die. Over a large number of rolls, we
should expect to obtain an average of 3.5 on the die (even though it's not possible to roll a 3.5). The
formula for expected value confirms that .
More generally, a random variable for which every one of a number of equally spaced outcomes has the
same probability is called a uniform random variable (in the die example, this "equal spacing" is
equal to 1). We can generalize our die example to find that if is a uniform random variable with
minimum possible value and maximum possible value , then . You may also wish to
verify that for the dice example, if is the random variable associated with the outcome of a second
die roll, then .
Given: Six positive integers, each of which does not exceed 20,000. The integers correspond to the
number of couples in a population possessing each genotype pairing for a given factor. In order, the six
given integers represent the number of couples having the following genotypes:
1. AA-AA
2. AA-Aa
3. AA-aa
4. Aa-Aa
5. Aa-aa
6. aa-aa
Return: The expected number of offspring displaying the dominant phenotype in the next
generation, under the assumption that every couple has exactly two offspring.
Sample Dataset
1 0 0 1 0 1
Sample Output
3.5
Problem 20
Finding a Shared Motif
Searching Through the Haystack
In “Finding a Motif in DNA”, we searched a given genetic string for a motif;;
however, this problem assumed that we know the motif in advance. In practice,
biologists often do not know exactly what they are looking for. Rather, they must
hunt through several different genomes at the same time to identify regions of
similarity that may indicate genes shared by different organisms or species.
The simplest such region of similarity is a motif occurring without mutation in every one of a
collection of genetic strings taken from a database;; such a motif corresponds to a substring shared
by all the strings. We want to search for long shared substrings, as a longer motif will likely
indicate a greater shared function.
Problem
A common substring of a collection of strings is a substring of every member of the collection. We
say that a common substring is a longest common substring if there does not exist a longer
common substring. For example, "CG" is a common substring of "ACGTACGT" and "AACCGGTATA",
but it is not as long as possible;; in this case, "GTA" is a longest common substring of "ACGTACGT"
and "AACCGTATA".
Note that the longest common substring is not necessarily unique;; for a simple example, "AA" and
"CC" are both longest common substrings of "AACC" and "CCAA".
Given: A collection of ( ) DNA strings of length at most 1 kbp each in FASTA format.
Return: A longest common substring of the collection. (If multiple solutions exist, you may return
any single solution.)
Sample Dataset
>Rosalind_1
GATTACA
>Rosalind_2
TAGACCA
>Rosalind_3
ATACA
Sample Output
AC
Problem 21
Independent Alleles
Mendel's Second Law
Recall that Mendel's first law states that

for any factor, an individual randomly
assigns one of its two alleles to its
offspring. Yet this law does not state
anything regarding the relationship with which alleles for
different factors will be inherited.
After recording the results of crossing thousands of pea

plants for seven years, Mendel surmised that alleles for
different factors are inherited with no dependence on each
other. This statement has become his second law, also
known as the law of independent assortment.
What does it mean for factors to be "assorted Figure 1. Mendel's second law
dictates that every one of the 16
independently?" If we cross two organisms, then a possible assignments of parental
shortened form of independent assortment states that if we alleles is equally likely. The Punnett
look only at organisms having the same alleles for one square for two factors therefore
places each of these assignments
factor, then the inheritance of another factor should not in a cell of a 4 X 4 table. The
change. probability of an offspring's genome
is equal to the number of times it
For example, Mendel's first law states that if we cross two appears in the table, divided by 16.
organisms, then 1/4 of their offspring will be , 1/4
will be , and 1/2 will be . Now, say that we cross plants that are both heterozygous for two
factors, so that both of their genotypes may be written as . Next, examine only
offspring: Mendel's second law states that the same proportions of , , and individuals will
be observed in these offspring. The same fact holds for and offspring.
As a result, independence will allow us to say that the probability of an offspring is simply
equal to the probability of an offspring times the probability of a organism, i.e., 1/16.
Because of independence, we can also extend the idea of Punnett squares to multiple factors, as
shown in Figure 1. We now wish to quantify Mendel's notion of independence using probability.
Problem
Two events and are independent if is equal to . In other words,
the events do not influence each other, so that we may simply
calculate each of the individual probabilities separately and
then multiply.
More generally, random variables and are independent

if whenever and are respective events for and ,
and are independent (i.e.,
).
As an example of how helpful independence can be for

calculating probabilities, let and represent the numbers Figure 2. The probability of each
showing on two six-sided dice. Intuitively, the number of pips outcome for the sum of the values
on two rolled dice (black and white),
showing on one die should not affect the number showing on broken down depending on the
the other die. If we want to find the probability that is number of pips showing on each
die. You can verify that 18 of the 36
odd, then we don't need to draw a tree diagram and consider
equally probable possibilities result
all possibilities. We simply first note that for to be in an odd sum.
odd, either is even and is odd or is odd and is
even. In terms of probability,
. Using
independence, this becomes
, or .
You can verify this result in Figure 2, which shows all 36 outcomes for rolling two dice.
Given: Two positive integers ( ) and ( ). In this problem, we begin with Tom, who
in the 0th generation has genotype Aa Bb. Tom has two children in the 1st generation, each of whom
has two children, and so on. Each organism always mates with an organism having genotype Aa Bb.
Return: The probability that at least Aa Bb organisms will belong to the -th generation of Tom's
family tree (don't count the Aa Bb mates at each level). Assume that Mendel's second law holds for
the factors.
Sample Dataset
2 1
Sample Output
0.684
An Example of Dependent Random Variables
Two random variables are dependent if they are not

independent. For an example of dependent random
variables, recall our example in “Mendel's First Law” of
drawing two balls from a bag containing 3 red balls and 2
blue balls. If represents the color of the first ball drawn
and is the color of the second ball drawn (without
replacement), then let be the event " is red" and be
the event is blue. In this case, the probability tree
Figure 3. The probability of any
diagram illustrated in Figure 3 demonstrates that outcome (leaf) in a probability tree
. Yet we can also see that diagram is given by the product of
probabilities from the start of the tree
and . We can now to the outcome. For example, the
probability that X is blue and Y is red
see that . is equal to (2/5)(1/4), or 1/10.
Problem 22
Finding a Protein Motif
Motif Implies Function
As mentioned in “Translating RNA into

Protein”, proteins perform every practical
function in the cell. A structural and
functional unit of the protein is a domain:
in terms of the protein's primary structure, the domain is an
interval of amino acids that can evolve and function
independently.
Each domain usually corresponds to a single function of

the protein (e.g., binding the protein to DNA, creating or
breaking specific chemical bonds, etc.). Some proteins,
such as myoglobin and the Cytochrome complex, have
only one domain, but many proteins are multifunctional and Figure 1. The human cyclophilin
therefore possess several domains. It is even possible to family, as represented by the
artificially fuse different domains into a protein molecule structures of the isomerase
domains of some of its members.
with definite properties, creating a chimeric protein.
Just like species, proteins can evolve, forming homologous groups called protein families.
Proteins from one family usually have the same set of domains, performing similar functions;; see
Figure 1.
A component of a domain essential for its function is called a motif, a term that in general has the
same meaning as it does in nucleic acids, although many other terms are also used (blocks,
signatures, fingerprints, etc.) Usually protein motifs are evolutionarily conservative, meaning that
they appear without much change in different species.
Proteins are identified in different labs around the world and gathered into freely accessible
databases. A central repository for protein data is UniProt, which provides detailed protein
annotation, including function description, domain structure, and post-translational modifications.
UniProt also supports protein similarity search, taxonomy analysis, and literature citations.
Problem
To allow for the presence of its varying forms, a protein motif is represented by a shorthand as follows:
[XY] means "either X or Y" and {X} means "any amino acid except X." For example, the N-
glycosylation motif is written as N{P}[ST]{P}.
You can see the complete description and features of a particular protein by its access ID "uniprot_id"
in the UniProt database, by inserting the ID number into
http://www.uniprot.org/uniprot/uniprot_id
Alternatively, you can obtain a protein sequence in FASTA format by following
http://www.uniprot.org/uniprot/uniprot_id.fasta
For example, the data for protein B5ZC00 can be found at http://www.uniprot.org/uniprot/B5ZC00.
Given: At most 15 UniProt Protein Database access IDs.

Return: For each protein possessing the N-glycosylation motif, output its given access ID followed
by a list of locations in the protein string where the motif can be found.
Sample Dataset
A2Z669
B5ZC00
P07204_TRBM_HUMAN
P20840_SAG1_YEAST
Sample Output
B5ZC00
85 118 142 306 395
P07204_TRBM_HUMAN
47 115 116 382 409
P20840_SAG1_YEAST
79 109 135 248 306 348 364 402 485 501 614
Note
Some entries in UniProt have one primary (citable) accession number and some secondary
numbers, appearing due to merging or demerging entries. In this problem, you may be given any
type of ID. If you type the secondary ID into the UniProt query, then you will be automatically
redirected to the page containing the primary ID. You can find more information about UniProt IDs
here.
Problem 23
Inferring mRNA from Protein
Pitfalls of Reversing Translation
When researchers discover a new protein, they would like to infer the strand of mRNA from which
this protein could have been translated, thus allowing them to locate genes associated with this
protein on the genome.
Unfortunately, although any RNA string can be translated into a unique protein
string, reversing the process yields a huge number of possible RNA strings from a
single protein string because most amino acids correspond to multiple RNA
codons (see the RNA Codon Table).
Because of memory considerations, most data formats that are built into
languages have upper bounds on how large an integer can be: in some versions of Python, an "int"
variable may be required to be no larger than , or 2,147,483,647. As a result, to deal with
very large numbers in Rosalind, we need to devise a system that allows us to manipulate large
numbers without actually having to store large numbers.
Problem
For positive integers and , modulo (written in shorthand) is the remainder when
is divided by . For example, because .
Modular arithmetic is the study of addition, subtraction, multiplication, and division with respect to
the modulo operation. We say that and are congruent modulo if ;;
in this case, we use the notation .
Two useful facts in modular arithmetic are that if and , then
and . To check your understanding of these
rules, you may wish to verify these relationships for , , , , and .
As you will see in this exercise, some Rosalind problems will ask for a (very large) integer solution
modulo a smaller number to avoid the computational pitfalls that arise with storing such large numbers.
Given: A protein string of length at most 1000 aa.

Return: The total number of different RNA strings from which the protein could have been
translated, modulo 1,000,000. (Don't neglect the importance of the stop codon in protein translation.)
Sample Dataset
MA
Sample Output
12
Hint
What does it mean intuitively to take a number modulo 1,000,000?
Problem 24
Open Reading Frames
Transcription May Begin Anywhere
In “Transcribing DNA into RNA”, we

discussed the transcription of DNA into
RNA, and in “Translating RNA into
Protein”, we examined the translation of
RNA into a chain of amino acids for the construction of
proteins. We can view these two processes as a single
step in which we directly translate a DNA string into a
protein string, thus calling for a DNA codon table.
However, three immediate wrinkles of complexity arise

Figure 1. Schematic image of the
when we try to pass directly from DNA to proteins. First, particular ORF with start and stop
not all DNA will be transcribed into RNA: so-called junk codons shown.
DNA appears to have no practical purpose for cellular
function. Second, we can begin translation at any position along a strand of RNA, meaning that any
substring of a DNA string can serve as a template for translation, as long as it begins with a start
codon, ends with a stop codon, and has no other stop codons in the middle. See Figure 1. As a
result, the same RNA string can actually be translated in three different ways, depending on how
we group triplets of symbols into codons. For example, ...AUGCUGAC... can be translated as
...AUGCUG..., ...UGCUGA..., and ...GCUGAC..., which will typically produce wildly different
protein strings.
Problem
Either strand of a DNA double helix can serve as the coding strand for RNA transcription. Hence, a
given DNA string implies six total reading frames, or ways in which the same region of DNA can be
translated into amino acids: three reading frames result from reading the string itself, whereas three
more result from reading its reverse complement.
An open reading frame (ORF) is one which starts from the start codon and ends by stop codon,
without any other stop codons in between. Thus, a candidate protein string is derived by translating an
open reading frame into amino acids until a stop codon is reached.
Given: A DNA string of length at most 1 kbp in FASTA format.
Return: Every distinct candidate protein string that can be translated from ORFs of . Strings can
be returned in any order.
Sample Dataset
>Rosalind_99
AGCCATGTAGCTAACTCAGGTTACATGGGGATGACCCCGCGACTTGGATTAGAGTCTCTTTTGGAATAAGC
CTGAATGATCCGAGTAGCATCTCAG
Sample Output
MLLGSFRLIPKETLIQVAGSSPCNLS
M
MGMTPRLGLESLLE
MTPRLGLESLLE
Problem 25
Enumerating Gene Orders
Rearrangements Power Large-Scale Genomic Changes
Point mutations can create changes in

populations of organisms from the same
species, but they lack the power to
create and differentiate entire species.
This more arduous work is left to larger mutations called
genome rearrangements, which move around huge
blocks of DNA. Rearrangements cause major genomic
change, and most rearrangements are fatal or seriously
damaging to the mutated cell and its descendants (many Figure 1. Similar regions in mouse
cancers derive from rearrangements). For this reason, and human chromosomes. Image
credit: U.S. Department of Energy
rearrangements that come to influence the genome of an Human Genome Program
entire species are very rare.
Because rearrangements that affect species evolution occur infrequently, two closely related
species will have very similar genomes. Thus, to simplify comparison of two such genomes,
researchers first identify similar intervals of DNA from the species, called synteny blocks;; over
time, rearrangements have created these synteny blocks and heaved them around across the two
genomes (often separating blocks onto different chromosomes, see Figure 1.).
A pair of synteny blocks from two different species are not strictly identical (they are separated by
the action of point mutations or very small rearrangements), but for the sake of studying large-scale
rearrangements, we consider them to be equivalent. As a result, we can label each synteny block
with a positive integer;; when comparing two species' genomes/chromosomes, we then only need to
specify the order of its numbered synteny blocks.
Problem
A permutation of length is an ordering of the positive integers . For example,
is a permutation of length .
Given: A positive integer .
Return: The total number of permutations of length , followed by a list of all such permutations (in
any order).
Sample Dataset
3
Sample Output
6
1 2 3
1 3 2
2 1 3
2 3 1
3 1 2
3 2 1
Problem 26
Calculating Protein Mass
Chaining the Amino Acids
In “Translating RNA into Protein”, we

examined the translation of RNA into an
amino acid chain for the construction of a
protein. When two amino acids link
together, they form a peptide bond, which releases a
molecule of water;; see Figure 1. Thus, after a series of
amino acids have been linked together into a polypeptide,
every pair of adjacent amino acids has lost one molecule of
water, meaning that a polypeptide containing amino
acids has had water molecules removed.
Figure 1. Formation of a peptide
More generally, a residue is a molecule from which a bond
water molecule has been removed;; every amino acid in a
protein are residues except the leftmost and the rightmost
ones. These outermost amino acids are special in that one
has an "unstarted" peptide bond, and the other has an
"unfinished" peptide bond. Between them, the two
molecules have a single "extra" molecule of water (see the
atoms marked in blue in Figure 2). Thus, the mass of a
protein is the sum of masses of all its residues plus the
mass of a single water molecule.
There are two standard ways of computing the mass of a
residue by summing the masses of its individual atoms. Its Figure 2. Outermost acids
monoisotopic mass is computed by using the principal
(most abundant) isotope of each atom in the amino acid, whereas its average mass is taken by
taking the average mass of each atom in the molecule (over all naturally appearing isotopes).
Many applications in proteomics rely on mass spectrometry, an analytical chemical technique
used to determine the mass, elemental composition, and structure of molecules. In mass
spectrometry, monoisotopic mass is used more often than average mass, and so all amino acid
masses are assumed to be monoisotopic unless otherwise stated.
The standard unit used in mass spectrometry for measuring mass is the atomic mass unit, which
is also called the dalton (Da) and is defined as one twelfth of the mass of a neutral atom of carbon-
12. The mass of a protein is the sum of the monoisotopic masses of its amino acid residues plus
the mass of a single water molecule (whose monoisotopic mass is 18.01056 Da).
In the following several problems on applications of mass spectrometry, we avoid the complication
of having to distinguish between residues and non-residues by only considering peptides excised
from the middle of the protein. This is a relatively safe assumption because in practice, peptide
analysis is often performed in tandem mass spectrometry. In this special class of mass
spectrometry, a protein is first divided into peptides, which are then broken into ions for mass
analysis.
Problem
In a weighted alphabet, every symbol is assigned a positive real number called a weight. A string
formed from a weighted alphabet is called a weighted string, and its weight is equal to the sum of
the weights of its symbols.
The standard weight assigned to each member of the 20-symbol amino acid alphabet is the
monoisotopic mass of the corresponding amino acid.
Given: A protein string of length at most 1000 aa.

Return: The total weight of . Consult the monoisotopic mass table.
Sample Dataset
SKADYEK
Sample Output
821.392
Problem 27
Locating Restriction Sites
The Billion-Year War
The war between viruses and bacteria has been waged for over a billion years.
Viruses called bacteriophages (or simply phages) require a bacterial host to
propagate, and so they must somehow infiltrate the bacterium;; such deception
can only be achieved if the phage understands the genetic framework underlying
the bacterium's cellular functions. The phage's goal is to insert DNA that will be replicated within
the bacterium and lead to the reproduction of as many copies of the phage as possible, which
sometimes also involves the bacterium's demise.
To defend itself, the bacterium must either obfuscate its
cellular functions so that the phage cannot infiltrate it, or
better yet, go on the counterattack by calling in the air
force. Specifically, the bacterium employs aerial scouts
called restriction enzymes, which operate by cutting
through viral DNA to cripple the phage. But what kind of
DNA are restriction enzymes looking for?
The restriction enzyme is a homodimer, which means

that it is composed of two identical substructures. Each of
these structures separates from the restriction enzyme in
order to bind to and cut one strand of the phage DNA Figure 1. DNA cleaved by EcoRV
molecule;; both substructures are pre-programmed with the restriction enzyme
same target string containing 4 to 12 nucleotides to search
for within the phage DNA (see Figure 1.). The chance that both strands of phage DNA will be cut
(thus crippling the phage) is greater if the target is located on both strands of phage DNA, as close
to each other as possible. By extension, the best chance of disarming the phage occurs when the
two target copies appear directly across from each other along the phage DNA, a phenomenon that
occurs precisely when the target is equal to its own reverse complement. Eons of evolution have
made sure that most restriction enzyme targets now have this form.
Problem
A DNA string is a reverse palindrome if it is equal to its
reverse complement. For instance, GCATGC is a reverse
palindrome because its reverse complement is GCATGC. See
Figure 2.
Figure 2. Palindromic recognition
Given: A DNA string of length at most 1 kbp in FASTA site
format.
Return: The position and length of every reverse palindrome in the string having length between 4
and 12. You may return these pairs in any order.
Sample Dataset
>Rosalind_24
TCAATGCATGCGGGTCTATATGCAT
Sample Output
4 6
5 4
6 6
7 4
17 4
18 4
20 6
21 4
Extra Information
You may be curious how the bacterium prevents its own DNA from being cut by restriction
enzymes. The short answer is that it locks itself from being cut through a chemical process called
DNA methylation.
Problem 28
RNA Splicing
Genes are Discontiguous
In “Transcribing DNA into RNA”, we

mentioned that a strand of DNA is copied
into a strand of RNA during transcription,
Figure 1. The elongation of a pre-
but we neglected to mention how
mRNA by RNAP as it moves down
transcription is achieved. the template strand of DNA.
In the nucleus, an enzyme (i.e., a molecule that

accelerates a chemical reaction) called RNA polymerase
(RNAP) initiates transcription by breaking the bonds joining
complementary bases of DNA. It then creates a molecule
called precursor mRNA, or pre-mRNA, by using one of
Figure 2. RNA is identical to the
the two strands of DNA as a template strand: moving coding strand except for the
down the template strand, when RNAP encounters the replacement of thymine with uracil.
next nucleotide, it adds the complementary base to the
growing RNA strand, with the provision that uracil must be used in place of thymine;; see Figure 1.
Because RNA is constructed based on complementarity, the second strand of DNA, called the
coding strand, is identical to the new strand of RNA except for the replacement of thymine with
uracil. See Figure 2 and recall “Transcribing DNA into RNA”.
After RNAP has created several nucleotides of RNA, the first separated complementary DNA bases
then bond back together. The overall effect is very similar to a pair of zippers traversing the DNA
double helix, unzipping the two strands and then quickly zipping them back together while the
strand of pre-mRNA is produced.
For that matter, it is not the case that an entire substring of DNA is transcribed into RNA and then
translated into a peptide one codon at a time. In reality, a pre-mRNA is first chopped into smaller
segments called introns and exons;; for the purposes of protein translation, the introns are thrown
out, and the exons are glued together sequentially to produce a final strand of mRNA. This cutting
and pasting process is called splicing, and it is facilitated by a collection of RNA and proteins
called a spliceosome. The fact that the spliceosome is made of RNA and proteins despite
regulating the splicing of RNA to create proteins is just one manifestation of a molecular chicken-
and-egg scenario that has yet to be fully resolved.
In terms of DNA, the exons deriving from a gene are collectively known as the gene's coding
region.
Problem
After identifying the exons and introns of an RNA string, we only need to delete the introns and
concatenate the exons to form a new string ready for translation.
Given: A DNA string (of length at most 1 kbp) and a collection of substrings of acting as
introns. All strings are given in FASTA format.
Return: A protein string resulting from transcribing and translating the exons of . (Note: Only one
solution will exist for the dataset provided.)
Sample Dataset
>Rosalind_10
ATGGTCTACATAGCTGACAAACAGCACGTAGCAATCGGTCGAATCTCGAGAGGCATATGGTCACATGATCG
GTCGAGCGTGTTTCAAAGTTTGCGCCTAG
>Rosalind_12
ATCGGTCGAA
>Rosalind_15
ATCGGTCGAGCGTGT
Sample Output
MVYIADKQHVASREAYGHMFKVCA
Problem 29
Enumerating k-mers Lexicographically
Organizing Strings
When cataloguing a collection of genetic strings, we should have an established
system by which to organize them. The standard method is to organize strings as
they would appear in a dictionary, so that "APPLE" precedes "APRON", which in
turn comes before "ARMOR".
Problem
Assume that an alphabet has a predetermined order;; that is, we write the alphabet as a
permutation , where . For instance, the English
alphabet is organized as .
Given two strings and having the same length , we say that precedes in the lexicographic
order (and write ) if the first symbol that doesn't match satisfies in .
Given: A collection of at most 10 symbols defining an ordered alphabet, and a positive integer (
).
Return: All strings of length that can be formed from the alphabet, ordered lexicographically.
Sample Dataset
T A G C
2
Sample Output
TT
TA
TG
TC
AT
AA
AG
AC
GT
GA
GG
GC
CT
CA
CG
CC
Note
As illustrated in the sample, the alphabet order in this problem is defined by the order in which
symbols are provided in the dataset, which is not necessarily the traditional order of the English
alphabet.
Problem 30
Longest Increasing Subsequence
A Simple Measure of Gene Order Similarity
In “Enumerating Gene Orders”, we started talking about comparing the order of
genes on a chromosome taken from two different species and moved around by
rearrangements throughout the course of evolution.
One very simple way of comparing genes from two chromosomes is to search for the largest
collection of genes that are found in the same order in both chromosomes. To do so, we will need
to apply our idea of permutations. Say that two chromosomes share genes;; if we label the genes
of one chromosome by the numbers 1 through n in the order that they appear, then the second
chromosome will be given by a permutation of these numbered genes. To find the largest number of
genes appearing in the same order, we need only to find the largest collection of increasing
elements in the permutation.
Problem
A subsequence of a permutation is a collection of elements of the permutation in the order that they
appear. For example, (5, 3, 4) is a subsequence of (5, 1, 3, 4, 2).
A subsequence is increasing if the elements of the subsequence increase, and decreasing if the
elements decrease. For example, given the permutation (8, 2, 1, 6, 5, 7, 4, 3, 9), an increasing
subsequence is (2, 6, 7, 9), and a decreasing subsequence is (8, 6, 5, 4, 3). You may verify that these
two subsequences are as long as possible.
Given: A positive integer followed by a permutation of length .
Return: A longest increasing subsequence of , followed by a longest decreasing subsequence of
.
Sample Dataset
5
5 1 4 2 3
Sample Output
1 2 3
5 4 2
Citation
Adapted from Jones & Pevzner, *An Introduction to Bioinformatics Algorithms, Problem 6.48.
Problem 31
Genome Assembly as Shortest Superstring
Introduction to Genome Sequencing
Recall from “Computing GC Content” that almost all humans share approximately
99.9% of the same nucleotides on the genome. Thus, if we know only a few
complete genomes from the species, then we already possess an important key
to unlocking the species genome.
Determining an organism's complete genome (called

genome sequencing) forms a central task of
bioinformatics. Unfortunately, we still don't possess the
microscope technology to zoom into the nucleotide level
and determine the sequence of a genome's nucleotides,
one at a time. However, researchers can apply chemical
methods to generate and identify much smaller snippets of
DNA, called reads.
After obtaining a large collection of reads from multiple Figure 1. Fragment Assembly works
copies of the same genome, the aim is to reconstruct the by blasting many copies of the same
genome into smaller, identifiable
desired genome from these small pieces of DNA;; this reads, which are then used to
process is called fragment assembly (see Figure 1). computationally assemble one copy
of the genome.
Problem
For a collection of strings, a larger string containing every one of the smaller strings as a substring is
called a superstring.
By the assumption of parsimony, a shortest possible superstring over a collection of reads serves as a
candidate chromosome.
Given: At most 50 DNA strings whose length does not exceed 1 kbp in FASTA format (which
represent reads deriving from the same strand of a single linear chromosome).
The dataset is guaranteed to satisfy the following condition: there exists a unique way to reconstruct
the entire chromosome from these reads by gluing together pairs of reads that overlap by more than
half their length.
Return: A shortest superstring containing all the given strings (thus corresponding to a
reconstructed chromosome).
Sample Dataset
>Rosalind_56
ATTAGACCTG
>Rosalind_57
CCTGCCGGAA
>Rosalind_58
AGACCTGCCG
>Rosalind_59
GCCGGAATAC
Sample Output
ATTAGACCTGCCGGAATAC
Extra Information
Although the goal of fragment assembly is to produce an entire genome, in practice it is only
possible to construct several contiguous portions of each chromosome, called contigs.
Furthermore, the assumption made above that reads all derive from the same strand is also
practically unrealistic;; in reality, researchers will not know the strand of DNA from which a given
read has been sequenced.
Problem 32
Perfect Matchings and RNA Secondary Structures
Introduction to RNA Folding
Because RNA is single-stranded, you

may have wondered if the cytosine and
guanine bases bond to each other like in
DNA. The answer is yes, as do adenine
and uracil, and the resulting base pairs define the
secondary structure of the RNA molecule;; recall that its
primary structure is just the order of its bases.
In the greater three-dimensional world, the base pairing

interactions of an RNA molecule cause it to twist around Figure 1. A hairpin loop is formed
when consecutive elements from
on itself in a process called RNA folding. When two two different regions of an RNA
complementary intervals of bases located close to each molecule base pair.
other on the strand bond to each other, they form a
structure called a hairpin loop (or stem loop), shown in Figure 1.
The same RNA molecule may base pair differently at different points in time, thus adopting many
different secondary structures. Our eventual goal is to classify which of these structures are
practically feasible, and which are not. To this end, we will ask natural combinatorial questions
about the number of possible different RNA secondary structures. In this problem, we will first
consider the (impractical) simplified case in which every nucleotide forms part of a base pair in the
RNA molecule.
Problem
A matching in a graph is a collection of edges of for

which no node belongs to more than one edge in the
collection. See Figure 2 for examples of matchings. If
contains an even number of nodes (say ), then a matching Figure 2. Three matchings
(highlighted in red) shown in three
on is perfect if it contains edges, which is clearly the
different graphs.
maximum possible. An example of a graph containing a
perfect matching is shown in Figure 3.
First, let denote the complete graph on labeled nodes, in which every node is connected to
every other node with an edge, and let denote the total number of perfect matchings in . For a
given node , there are ways to join to the other nodes in the graph, after which point we
must form a perfect matching on the remaining nodes. This reasoning provides us with the
recurrence relation ;; using the fact that is 1, this recurrence relation
implies the closed equation .
Given an RNA string , a bonding graph for
is formed as follows. First, assign each symbol of to a node,
and arrange these nodes in order around a circle, connecting
them with edges called adjacency edges. Second, form all
possible edges {A, U} and {C, G}, called basepair edges;; we
will represent basepair edges with dashed edges, as
illustrated by the bonding graph in Figure 4.
Note that a matching contained in the basepair edges will

represent one possibility for base pairing interactions in , as
shown in Figure 5. For such a matching to exist, must have
the same number of 'A's as 'U's and the same number of 'C's
as 'G's. Figure 3. This graph contains 10
nodes;; the five edges forming a
Given: An RNA string of length at most 80 bp having the perfect matching on these nodes
same number of occurrences of 'A' as 'U' and the same are highlighted in red.
number of occurrences of 'C' as 'G'.
Return: The total possible number of perfect matchings of

basepair edges in the bonding graph of .
Sample Dataset
>Rosalind_23
AGCUAGUCAU
Sample Output
Figure 4. The bonding graph for the
RNA string s = UAGCGUGAUCAC.
12
Figure 5. A perfect matching on the

basepair edges is highlighted in red
and represents a candidate
secondary structure for the RNA
strand.
Problem 33
Partial Permutations
Partial Gene Orderings
Similar species will share many of the same genes, possibly with modifications.
Thus, we can compare two genomes by analyzing the orderings of their genes,
then inferring which rearrangements have separated the genes.
In “Enumerating Gene Orders”, we used permutations to model gene orderings. Yet two genomes
will have evolved along their own separate paths, and so they won't share all of the same genes. As
a result, we should modify the notion of permutation in order to quantify the notion of partial gene
orderings.
Problem
A partial permutation is an ordering of only objects taken from a collection containing objects
(i.e., ). For example, one partial permutation of three of the first eight positive integers is given
by .
The statistic counts the total number of partial permutations of objects that can be formed
from a collection of objects. Note that is just the number of permutations of objects,
which we found to be equal to in “Enumerating Gene Orders”.
Given: Positive integers and such that and .
Return: The total number of partial permutations , modulo 1,000,000.
Sample Dataset
21 7
Sample Output
51200
Problem 34
Introduction to Random Strings
Modeling Random Genomes
We already know that the genome is not just a random strand of nucleotides;;
recall from “Finding a Motif in DNA” that motifs recur commonly across individuals
and species. If a DNA motif occurs in many different organisms, then chances are
good that it serves an important function.
At the same time, if you form a long enough DNA string, then you should theoretically be able to
locate every possible short substring in the string. And genomes are very long;; the human genome
contains about 3.2 billion base pairs. As a result, when analyzing an unknown piece of DNA, we
should try to ensure that a motif does not occur out of random chance.
To conclude whether motifs are random or not, we need to quantify the likelihood of finding a given
motif randomly. If a motif occurs randomly with high probability, then how can we really compare
two organisms to begin with? In other words, all very short DNA strings will appear randomly in a
genome, and very few long strings will appear;; what is the critical motif length at which we can
throw out random chance and conclude that a motif appears in a genome for a reason?
In this problem, our first step toward understanding random occurrences of strings is to form a
simple model for constructing genomes randomly. We will then apply this model to a somewhat
simplified exercise: calculating the probability of a given motif occurring randomly at a fixed location
in the genome.
Problem
An array is a structure containing an ordered collection of

objects (numbers, strings, other arrays, etc.). We let
denote the -th value in array . You may like to think of an
array as simply a matrix having only one row.
A random string is constructed so that the probability of Figure 1. The graph of the common
logarithm function of x. For a given x-
choosing each subsequent symbol is based on a fixed value, the corresponding y-value is
underlying symbol frequency. the exponent to which we must raise
10 to obtain x. Note that x-values
GC-content offers us natural symbol frequencies for between 0 and 1 get mapped to y-
constructing random DNA strings. If the GC-content is , then values between -infinity and 0.
we set the symbol frequencies of C and G equal to and the
symbol frequencies of A and T equal to . For example, if the GC-content is 40%, then as we
construct the string, the next symbol is 'G'/'C' with probability 0.2, and the next symbol is 'A'/'T' with
probability 0.3.
In practice, many probabilities wind up being very small. In order to work with small probabilities, we
may plug them into a function that "blows them up" for the sake of comparison. Specifically, the
common logarithm of (defined for and denoted ) is the exponent to which we
must raise 10 to obtain .
See Figure 1 for a graph of the common logarithm function . In this graph, we can see
that the logarithm of -values between 0 and 1 always winds up mapping to -values between
and 0: -values near 0 have logarithms close to , and -values close to 1 have logarithms close
to . Thus, we will select the common logarithm as our function to "blow up" small probability values
for comparison.
Given: A DNA string of length at most 100 bp and an array containing at most 20 numbers
between 0 and 1.
Return: An array having the same length as in which represents the common logarithm
of the probability that a random string constructed with the GC-content found in will match
exactly.
Sample Dataset
ACGATACAA
0.129 0.287 0.423 0.476 0.641 0.742 0.783
Sample Output
-‐5.737 -‐5.217 -‐5.263 -‐5.360 -‐5.958 -‐6.628 -‐7.009
Hint
One property of the logarithm function is that for any positive numbers and ,
.
Problem 35
Enumerating Oriented Gene Orderings
Synteny Blocks Have Orientations
In “Enumerating Gene Orders”, we introduced synteny blocks for two different
species, which are very similar areas of two species genomes that have been
flipped and moved around by rearrangements. In that problem, we used the
permutation to model the order of synteny blocks on a single chromosome.
However, each strand of a DNA molecule has an orientation (as RNA transcription only occurs in
one direction), and so to more prudently model chromosomes using synteny blocks, we should
provide each block with an orientation to indicate the strand on which it is located. Adding
orientations to synteny blocks requires us to expand our notion of permutation so that each index
in the permutation has its own orientation.
Problem
A signed permutation of length is some ordering of the positive integers in which
each integer is then provided with either a positive or negative sign (for the sake of simplicity, we omit
the positive sign). For example, is a signed permutation of length .
Return: The total number of signed permutations of length , followed by a list of all such
permutations (you may list the signed permutations in any order).
Sample Dataset
Sample Output
8
-‐1 -‐2
-‐1 2
1 -‐2
1 2
-‐2 -‐1
-‐2 1
2 -‐1
2 1
Problem 36
Finding a Spliced Motif
Motifs Are Rarely Contiguous
In “Finding a Motif in DNA”, we searched for occurrences of a motif as a substring
of a larger database genetic string. However, because a DNA strand coding for a
protein is often interspersed with introns (see “RNA Splicing”), we need a way to
recognize a motif that has been chopped up into pieces along a chromosome.
Problem
A subsequence of a string is a collection of symbols contained in order (though not necessarily
contiguously) in the string (e.g., ACG is a subsequence of TATGCTAAGATC). The indices of a
subsequence are the positions in the string at which the symbols of the subsequence appear;; thus,
the indices of ACG in TATGCTAAGATC can be represented by (2, 5, 9).
As a substring can have multiple locations, a subsequence can have multiple collections of indices,
and the same index can be reused in more than one appearance of the subsequence;; for example,
ACG is a subsequence of AACCGGTT in 8 different ways.
Given: Two DNA strings and (each of length at most 1 kbp) in FASTA format.
Return: One collection of indices of in which the symbols of appear as a subsequence of . If
multiple solutions exist, you may return any one.
Sample Dataset
>Rosalind_14
ACGTACGTGACG
>Rosalind_18
GTA
Sample Output
3 8 10
Extra Information
For the mathematically inclined, we may equivalently say that is a subsequence
of if the characters of appear in the same order within . Even more formally, a
subsequence of is a string , where .
Problem 37
Transitions and Transversions
Certain Point Mutations are More Common
Point mutations occurring in DNA can be

divided into two types: transitions and
transversions. A transition substitutes
one purine for another ( ) or one
pyrimidine for another ( );; that is, a transition does
not change the structure of the nucleobase. Conversely, a
transversion is the interchange of a purine for a pyrimidine
base, or vice-versa. See Figure 1. Transitions and
transversions can be defined analogously for RNA
mutations.
Because transversions require a more drastic change to

the base's chemical structure, they are less common than Figure 1. Illustration of transitions
transitions. Across the entire genome, the ratio of and transversions.
transitions to transversions is on average about 2.
However, in coding regions, this ratio is typically higher (often exceeding 3) because a transition
appearing in coding regions happens to be less likely to change the encoded amino acid,
particularly when the substituted base is the third member of a codon (feel free to verify this fact
using the DNA codon table). Such a substitution, in which the organism's protein makeup is
unaffected, is known as a silent substitution.
Because of its potential for identifying coding DNA, the ratio of transitions to transversions between
two strands of DNA offers a quick and useful statistic for analyzing genomes.
Problem
For DNA strings and having the same length, their transition/transversion ratio is
the ratio of the total number of transitions to the total number of transversions, where symbol
substitutions are inferred from mismatched corresponding symbols as when calculating Hamming
distance (see “Counting Point Mutations”).
Given: Two DNA strings and of equal length (at most 1 kbp).
Return: The transition/transversion ratio .

Sample Dataset
>Rosalind_0209
GCAACGCACAACGAAAACCCTTAGGGACTGGATTATTTCGTGATCGTTGTAGTTATTGGA
AGTACGGGCATCAACCCAGTT
>Rosalind_2200
TTATCTGACAAAGAAAGCCGTCAACGGCTGGATAATTTCGCGATCGTGCTGGTTACTGGC
GGTACGAGTGTTCCTTTGGGT
Sample Output
1.21428571429
Problem 38
Completing a Tree
The Tree of Life
"As buds give rise by growth to fresh

buds, and these, if vigorous, branch out
and overtop on all sides many a feebler
branch, so by generation I believe it has
been with the great Tree of Life, which fills with its dead
and broken branches the crust of the earth, and covers the
surface with its ever-branching and beautiful ramifications."
Charles Darwin, The Origin of Species
A century and a half has passed since the publication of Figure 1. A phylogeny illustrating
proposed evolutionary relationships
Darwin's magnum opus, and yet the construction of a among the three domains of life:
single Tree of Life uniting life on Earth still has not been Bacteria, Archaea, and Eukaryota.
completed, with perhaps as many as 90% of all living
species not yet catalogued (although a beautiful interactive animation has been produced by
OneZoom).
To get an insight about state-of-art attempts to build this tree, you may take a look at the Tree of
Life Web Project - collaborative effort of biologists from around the world to combine information
about diversity of life on Earth. It is a peer-reviewed ongoing project started in 1995, now it holds
more than 10,000 pages with characteristics of different groups of organisms and their evolutionary
history, and tree still grows.
Instead of trying to construct the entire Tree of Life all at once, we often wish to form a simpler tree
in which a collection of species have been clumped together for the sake of simplicity;; such a
group is called a taxon (pl. taxa). For a given collection of taxa, a phylogeny is a treelike diagram
that best represents the evolutionary connections between the taxa: the construction of a particular
phylogeny depends on our specific assumptions regarding how these evolutionary relationships
should be interpreted. See Figure 1.
Problem
An undirected graph is connected if there is a path

connecting any two nodes. A tree is a connected (undirected)
graph containing no cycles;; this definition forces the tree to
have a branching structure organized around a central core of
nodes, just like its living counterpart. See Figure 2.
We have already grown familiar with trees in “Mendel's First

Law”, where we introduced the probability tree diagram to
visualize the outcomes of a random variable.
In the creation of a phylogeny, taxa are encoded by the tree's
leaves, or nodes having degree 1. A node of a tree having
degree larger than 1 is called an internal node. Figure 2. A labeled tree with 6
vertices and 5 edges.
Given: A positive integer ( ) and an adjacency
list corresponding to a graph on nodes that contains no
cycles.
Return: The minimum number of edges that can be added to the graph to produce a tree.
Sample Dataset
10
1 2
2 8
4 10
5 9
6 10
7 9
Sample Output
Extra Information
After solving this problem, a standard mathematical exercise for the technically minded is to verify
that every tree having 2 or more nodes must contain at least two leaves.
Problem 39
Catalan Numbers and RNA Secondary Structures
The Human Knot
You may have had the misfortune to

participate in a team-building event that
featured the "human knot," in which
everyone joins hands with two other
people, and the group must undo the giant knot of arms
without letting go (see Figure 1).
Let's consider a simplified version of the human knot. Say

that we have an even number of people at a party who are
standing in a circle, and they pair off and shake hands at Figure 1. Knot fun. Courtesy El Photo
the same time. One combinatorial question at hand asks Studio.
us to count the total number of ways that the guests can
shake hands without any two pairs interfering with each
other by crossing arms.
This silly little counting problem is actually an excellent

analogy for RNA folding. In practice, base pairing can
occur anywhere along the RNA molecule, but the
secondary structure of RNA often forbids base pairs
crossing over each other, which forms a structure called a Figure 2. This pseudoknot was
formed when bonding occurred at
pseudoknot (see Figure 2)). Pseudoknots are not the endpoints of overlapping
technically knots, but they nevertheless cause RNA to fold intervals [1,3] and [2, 4].
over itself.
Forbidding pseudoknots offers an interesting wrinkle to the problem of counting potential RNA
secondary structures that we started working with in “Perfect Matchings and RNA Secondary
Structures”, in which every possible nucleotide of a strand of RNA must base pair with another
nucleotide.
Problem
A matching in a graph is noncrossing if none of its edges
cross each other. If we assume that the nodes of this graph
are arranged around a circle, and if we label these nodes with
positive integers between 1 and , then a matching is
noncrossing as long as there are not edges and
such that .
Figure 3. The only two noncrossing
A noncrossing matching of basepair edges in the bonding perfect matchings of basepair
graph corresponding to an RNA string will correspond to a edges (shown in red) for the RNA
string UAGCGUGAUCAC.
possible secondary structure of the underlying RNA strand
that lacks pseudoknots, as shown in Figure 3.
In this problem, we will consider counting noncrossing perfect

matchings of basepair edges. As a motivating example of how
to count noncrossing perfect matchings, let denote the
number of noncrossing perfect matchings in the complete
graph . After setting , we can see that should
equal 1 as well. As for the case of a general , say that the
nodes of are labeled with the positive integers from 1 to
. We can join node 1 to any of the remaining
Figure 4. This figure shows all
nodes;; yet once we have chosen this node (say ), we possible noncrossing perfect
cannot add another edge to the matching that crosses the matchings in complete graphs on 2,
edge . As a result, we must match all the edges on 4, 6, and 8 nodes;; the total number
of such matchings are 1, 2, 5, and
one side of to each other. This requirement forces 14, respectively. Courtesy Tom
to be even, so that we can write for some positive Davis.
integer .
There are nodes on one side of and nodes on the other side of , so
that in turn there will be different ways of forming a perfect matching on the remaining
nodes of . If we let vary over all possible choices of even numbers between 1 and ,
then we obtain the recurrence relation . The resulting numbers counting
noncrossing perfect matchings in are called the Catalan numbers, and they appear in a huge
number of other settings. See Figure 4 for an illustration counting the first four Catalan numbers.
Given: An RNA string having the same number of occurrences of 'A' as 'U' and the same number
of occurrences of 'C' as 'G'. The length of the string is at most 300 bp.
Return: The total number of noncrossing perfect matchings of basepair edges in the bonding graph
of , modulo 1,000,000.
Sample Dataset
>Rosalind_57
AUAU
Sample Output
Hint
Write a function that counts Catalan numbers via dynamic programming. How can we modify this
function to apply to our given problem?
Problem 40
Error Correction in Reads
Genome Sequencing Isn't Perfect
In “Genome Assembly as Shortest Superstring”, we introduce the problem of
assembling a genome from a collection of reads. Even though genome
sequencing is a multi-billion dollar enterprise, sequencing machines that identify
reads still produce errors a substantial percentage of the time. To make matters
worse, these errors are unpredictable;; it is difficult to determine if the machine has made an error,
let alone where in the read the error has occurred. For this reason, error correction in reads is
typically a vital first step in genome assembly.
Problem
As is the case with point mutations, the most common type of sequencing error occurs when a single
nucleotide from a read is interpreted incorrectly.
Given: A collection of up to 1000 reads of equal length (at most 50 bp) in FASTA format. Some of
these reads were generated with a single-nucleotide error. For each read in the dataset, one of the
following applies:
was correctly sequenced and appears in the dataset at least twice (possibly as a reverse
complement);;
is incorrect, it appears in the dataset exactly once, and its Hamming distance is 1 with respect
to exactly one correct read in the dataset (or its reverse complement).
Return: A list of all corrections in the form "[old read]->[new read]". (Each correction must be a
single symbol substitution, and you may return the corrections in any order.)
Sample Dataset
>Rosalind_52
TCATC
>Rosalind_44
TTCAT
>Rosalind_68
TCATC
>Rosalind_28
TGAAA
>Rosalind_95
GAGGA
>Rosalind_66
TTTCA
>Rosalind_33
ATCAA
>Rosalind_21
TTGAT
>Rosalind_18
TTTCC
Sample Output
TTCAT-‐>TTGAT
GAGGA-‐>GATGA
TTTCC-‐>TTTCA
Problem 41
Counting Phylogenetic Ancestors
Culling the Forest
In “Completing a Tree”, we introduced the

tree for the purposes of constructing
phylogenies. Yet the definition of tree as
a connected graph with no cycles
produces a huge class of different graphs, from simple Figure 1. Trees come in lots of
paths and star-like graphs to more familiar arboreal different shapes.
structures (see Figure 1). Which of these graphs are
appropriate for phylogenetic study?
Modern evolutionary theory (beginning with Darwin) indicates that the only way a new species can
be created is if it splits off from an existing species after a population is isolated for an extended
period of time. This model of species evolution implies a very specific type of phylogeny, in which
internal nodes represent branching points of evolution where an ancestor species either evolved into
a new species or split into two new species: therefore, one edge of this internal node therefore
connects the node to its most recent ancestor, whereas one or two new edges connect it to its
immediate descendants. This framework offers a much clearer notion of how to characterize
phylogenies.
Problem
A binary tree is a tree in which each node has degree equal to at most 3. The binary tree will be our
main tool in the construction of phylogenies.
A rooted tree is a tree in which one node (the root) is set aside to serve as the pinnacle of the tree. A
standard graph theory exercise is to verify that for any two nodes of a tree, exactly one path connects
the nodes. In a rooted tree, every node will therefore have a single parent, or the unique node
such that the path from to the root contains . Any other node adjacent to is called a
child of because must be the parent of ;; note that a node may have multiple children. In other
words, a rooted tree possesses an ordered hierarchy from the root down to its leaves, and as a result,
we may often view a rooted tree with undirected edges as a directed graph in which each edge is
oriented from parent to child. We should already be familiar with this idea;; it's how the Rosalind
problem tree works!
Even though a binary tree can include nodes having degree 2, an unrooted binary tree is defined
more specifically: all internal nodes have degree 3. In turn, a rooted binary tree is such that only the
root has degree 2 (all other internal nodes have degree 3).
Given: A positive integer ( ).
Return: The number of internal nodes of any unrooted binary tree having leaves.
Sample Dataset
Sample Output
2
Hint
In solving “Completing a Tree”, you may have formed the conjecture that a graph with no cycles and
nodes is a tree precisely when it has edges. This is indeed a theorem of graph theory.
Problem 42
k-Mer Composition
Generalizing GC-Content
A length substring of a genetic string is

commonly called a k-mer. A genetic
Figure 1. The 2-mer composition of
string of length can be seen as TTGATTACCTTATTTGATCATTACACATTGTACGCTT
composed of overlapping k-
mers. The k-mer composition of a genetic string encodes the number of times that each possible
k-mer occurs in the string. See Figure 1. The 1-mer composition is a generalization of the GC-
content of a strand of DNA, and the 2-mer, 3-mer, and 4-mer compositions of a DNA string are also
commonly known as its di-nucleotide, tri-nucleotide, and tetra-nucleotide compositions.
The biological significance of k-mer composition is manyfold. GC-content is helpful not only in
helping to identify a piece of unknown DNA (see “Computing GC Content”), but also because a
genomic region having high GC-content compared to the rest of the genome signals that it may
belong to an exon. Analyzing k-mer composition is vital to fragment assembly as well.
In “Computing GC Content”, we also drew an analogy between analyzing the frequency of
characters and identifying the underlying language. For larger values of , the k-mer composition
offers a more robust fingerprint of a string's identity because it offers an analysis on the scale of
substrings (i.e., words) instead of that of single symbols. As a basis of comparison, in language
analysis, the k-mer composition of a text can be used not only to pin down the language, but also
often the author.
Problem
For a fixed positive integer , order all possible k-mers taken from an underlying alphabet
lexicographically.
Then the k-mer composition of a string can be represented by an array for which denotes
the number of times that the th k-mer (with respect to the lexicographic order) appears in .
Given: A DNA string in FASTA format (having length at most 100 kbp).
Return: The 4-mer composition of .
Sample Dataset
>Rosalind_6431
CTTCGAAAGTTTGGGCCGAGTCTTACAGTCGGTCTTGAAGCAAAGTAACGAACTCCACGG
CCCTGACTACCGAACCAGTTGTGAGTACTCAACTGGGTGAGAGTGCAGTCCCTATTGAGT
TTCCGAGACTCACCGGGATTTTCGATCCAGCCTCAGTCCAGTCTTGTGGCCAACTCACCA
AATGACGTTGGAATATCCCTGTCTAGCTCACGCAGTACTTAGTAAGAGGTCGCTGCAGCG
GGGCAAGGAGATCGGAAAATGTGCTCTATATGCGACTAAAGCTCCTAACTTACACGTAGA
CTTGCCCGTGTTAAAAACTCGGCTCACATGCTGTCTGCGGCTGGCTGTATACAGTATCTA
CCTAATACCCTTCAGTTCGCCGCACAAAAGCTGGGAGTTACCGCGGAAATCACAG
Sample Output
4 1 4 3 0 1 1 5 1 3 1 2 2 1 2 0 1 1 3 1 2 1 3 1 1 1 1 2 2 5 1 3 0 2 2 1
1 1 1 3 1 0 0 1 5 5 1 5 0 2 0 2 1 2 1 1 1 2 0 1 0 0 1 1 3 2 1 0 3 2 3
0 0 2 0 8 0 0 1 0 2 1 3 0 0 0 1 4 3 2 1 1 3 1 2 1 3 1 2 1 2 1 1 1 2 3 2
1 1 0 1 1 3 2 1 2 6 2 1 1 1 2 3 3 3 2 3 0 3 2 1 1 0 0 1 4 3 0 1 5 0 2
0 1 2 1 3 0 1 2 2 1 1 0 3 0 0 4 5 0 3 0 2 1 1 3 0 3 2 2 1 1 0 2 1 0 2 2
1 2 0 2 2 5 2 2 1 1 2 1 2 2 2 2 1 1 3 4 0 2 1 1 0 1 2 2 1 1 1 5 2 0 3
2 1 1 2 2 3 0 3 0 1 3 1 2 3 0 2 1 2 2 1 2 3 0 1 2 3 1 1 3 1 0 1 1 3 0 2
1 2 2 0 2 1 1
Problem 43
Speeding Up Motif Finding
Shortening the Motif Search
In “Finding a Motif in DNA”, we discussed the problem of searching a genome for
a known motif. Because of the large scale of eukaryotic genomes, we need to
accomplish this computational task as efficiently as possible.
The standard method for locating one string as a substring of another string (and perhaps one
you implemented in “Finding a Motif in DNA”) is to move a sliding window across the larger string,
at each step starting at and matching subsequent symbols of to symbols of . After we have
located a match or mismatch, we then shift the window backwards to begin searching at .
The potential weakness of this method is as follows: say we have matched 100 symbols of to
before reaching a mismatch. The window-sliding method would then move back 99 symbols of
and start comparing to ;; can we avoid some of this sliding?
For example, say that we are looking for in

. From to , we have matched seven
symbols of , and yet = G produces a mismatch with = T. We don't need to go all the
way back to and start matching with because , , and are all
different from . What about ? Because , the previous
mismatch of and guarantees the same mismatch with and .
Following this analysis, we may advance directly to and continue sliding our window, without
ever having to move it backward.
This method can be generalized to form the framework behind the Knuth-Morris-Pratt algorithm
(KMP), which was published in 1977 and offers an efficiency boost for determining whether a given
motif can be located within a larger string.
Problem
A prefix of a length string is a substring ;; a suffix of is a substring .
The failure array of is an array of length for which is the length of the longest substring
that is equal to some prefix , where cannot equal (otherwise,
would always equal ). By convention, .
Given: A DNA string (of length at most 100 kbp) in FASTA format.
Return: The failure array of .
Sample Dataset
>Rosalind_87
CAGCATGGTATCACAGCAGAG
Sample Output
0 0 0 1 2 0 0 0 0 0 0 1 2 1 2 3 4 5 3 0 0
Extra Information
If you would like a more precise technical explanation of the Knuth-Morris-Pratt algorithm, please
take a look at this site
Problem 44
Finding a Shared Spliced Motif
Locating Motifs Despite Introns
In “Finding a Shared Motif”, we discussed searching through a database

containing multiple genetic strings to find a longest common substring of these
strings, which served as a motif shared by the two strings. However, as we saw in
“RNA Splicing”, coding regions of DNA are often interspersed by introns that do
not code for proteins.
We therefore need to locate shared motifs that are separated across exons, which means that the
motifs are not required to be contiguous. To model this situation, we need to enlist subsequences.
Problem
A string is a common subsequence of strings and if the symbols of appear in order as a
subsequence of both and . For example, "ACTG" is a common subsequence of "AACCTTGG" and
"ACACTGTGA".
Analogously to the definition of longest common substring, is a longest common subsequence of
and if there does not exist a longer common subsequence of the two strings. Continuing our above
example, "ACCTTG" is a longest common subsequence of "AACCTTGG" and "ACACTGTGA", as is
"AACTGG".
Given: Two DNA strings and (each having length at most 1 kbp) in FASTA format.
Return: A longest common subsequence of and . (If more than one solution exists, you may
return any one.)
Sample Dataset
>Rosalind_23
AACCTTGG
>Rosalind_64
ACACTGTGA
Sample Output
AACTGG
Problem 45
Ordering Strings of Varying Length Lexicographically
Organizing Strings of Different Lengths
In “Enumerating k-mers Lexicographically”, we introduced the lexicographic order

for strings of the same length constructed from some ordered underlying alphabet.
However, our experience with dictionaries suggests that we should be able to
order strings of different lengths just as easily. That is, we already have an
intuitive sense that "APPLE" comes before "APPLET", which comes before "ARTS," and so we
should be able to apply this intuition toward cataloguing genetic strings of varying lengths.
Problem
Say that we have strings and with . Consider the substring
. We have two cases:
1. If , then we set because is shorter than (e.g., ).

2. Otherwise, . We define if and define if (e.g.,
because ).
Given: A permutation of at most 12 symbols defining an ordered alphabet and a positive integer
( ).
Return: All strings of length at most formed from , ordered lexicographically. (Note: As in
“Enumerating k-mers Lexicographically”, alphabet order is based on the order in which the symbols are
given.)
Sample Dataset
D N A
3
Sample Output
D
DD
DDD
DDN
DDA
DN
DND
DNN
DNA
DA
DAD
DAN
DAA
N
ND
NDD
NDN
NDA
NN
NND
NNN
NNA
NA
NAD
NAN
NAA
A
AD
ADD
ADN
ADA
AN
AND
ANN
ANA
AA
AAD
AAN
AAA
Extra Information
We can combine conditions (1) and (2) above into a single condition by adding a blank character
to the beginning of our ordered alphabet. Then, if is shorter than , we simply add as many
instances of as necessary to make and the same length.
Problem 46
Maximum Matchings and RNA Secondary Structures
Breaking the Bonds
In “Perfect Matchings and RNA Secondary Structures”, we considered a problem

that required us to assume that every possible nucleotide is involved in base
pairing to induce an RNA secondary structure. Yet the only way this could occur
is if the frequency of adenine in our RNA strand is equal to the frequency of uracil
and if the same holds for guanine and cytosine.
We will therefore begin to explore ways of counting secondary structures in which this condition is
not required. A more general combinatorial problem will ask instead for the total number of
secondary structures of a strand having a maximum possible number of base pairs.
Problem
The graph theoretical analogue of the quandary stated in the
introduction above is that if we have an RNA string that does
not have the same number of 'C's as 'G's and the same
number of 'A's as 'U's, then the bonding graph of cannot
possibly possess a perfect matching among its basepair
edges. For example, see Figure 1;; in fact, most bonding
graphs will not contain a perfect matching. Figure 1. The bonding graph of s =
UAGCGUGAUCAC (left) has a
In light of this fact, we define a maximum matching in a perfect matching of basepair edges,
graph as a matching containing as many edges as possible. but this is not the case for t =
CAGCGUGAUCAC, in which one
See Figure 2 for three maximum matchings in graphs. symbol has been replaced.
A maximum matching of basepair edges will correspond to a
way of forming as many base pairs as possible in an RNA
string, as shown in Figure 3.
Given: An RNA string of length at most 100. Figure 2. A maximum matching
(highlighted in red) is shown in each
Return: The total possible number of maximum matchings of the three graphs above. Verify that
no other matching can contain more
of basepair edges in the bonding graph of .
edges.
Sample Dataset
>Rosalind_92
AUGCUUC
Sample Output
Figure 3. A red maximum matching

of basepair edges in the bonding
graph for t = CAGCGUGAUCAC.
Problem 47
Creating a Distance Matrix
Introduction to Distance-Based Phylogeny
A number of different approaches are used to build phylogenies, each one
featuring its own computational strengths and weaknesses. One of these
measures is distance-based phylogeny, which constructs a tree from
evolutionary distances calculated between pairs of taxa.
A wide assortment of different measures exist for quantifying this evolutionary distance. Once we
have selected a distance function and used it to calculate the distance between every pair of taxa,
we place these pairwise distance functions into a table.
In this problem, we will consider an evolutionary function based on Hamming distance. Recall from
“Counting Point Mutations” that this function compares two homologous strands of DNA by
counting the minimum possible number of point mutations that could have occurred on the
evolutionary path between the two strands.
Problem
For two strings and of equal length, the p-distance between them, denoted , is the
proportion of corresponding symbols that differ between and .
For a general distance function on taxa (taxa are often represented by genetic
strings), we may encode the distances between pairs of taxa via a distance matrix in which
.
Given: A collection of ( ) DNA strings of equal length (at most 1 kbp). Strings
are given in FASTA format.
Return: The matrix corresponding to the p-distance on the given strings. As always, note
that your answer is allowed an absolute error of 0.001.
Sample Dataset
>Rosalind_9499
TTTCCATTTA
>Rosalind_0942
GATTCATTTC
>Rosalind_6568
TTTCCATTTT
>Rosalind_1833
GTTCCATTTA
Sample Output
0.00000 0.40000 0.10000 0.10000

0.40000 0.00000 0.40000 0.30000
0.10000 0.40000 0.00000 0.20000
0.10000 0.30000 0.20000 0.00000
Problem 48
Reversal Distance
Rearrangements Power Large-Scale Genomic Changes
Perhaps the most common type of genome rearrangement is an inversion, which
flips an entire interval of DNA found on the same chromosome. As in the case of
calculating Hamming distance (see “Counting Point Mutations”), we would like to
determine the minimum number of inversions that have occurred on the
evolutionary path between two chromosomes. To do so, we will use the model introduced in
“Enumerating Gene Orders” in which a chromosome is represented by a permutation of its synteny
blocks.
Problem
A reversal of a permutation creates a new permutation by inverting some interval of the permutation;;
, , and are all reversals of . The reversal
distance between two permutations and , written , is the minimum number of reversals
required to transform into (this assumes that and have the same length).
Given: A collection of at most 5 pairs of permutations, all of which have length 10.
Return: The reversal distance between each permutation pair.
Sample Dataset
1 2 3 4 5 6 7 8 9 10
3 1 5 2 7 4 9 6 10 8
3 10 8 2 5 4 7 1 6 9
5 2 3 1 7 4 10 8 6 9
8 6 7 9 4 1 3 10 2 5
8 2 7 6 9 1 5 3 10 4
3 9 10 4 1 8 6 7 5 2
2 9 8 5 1 7 3 4 6 10
1 2 3 4 5 6 7 8 9 10
1 2 3 4 5 6 7 8 9 10
Sample Output
9 4 5 7 0
Hint
Don't be afraid to try an ugly solution.
Problem 49
Matching Random Motifs
More Random Strings
In “Introduction to Random Strings”, we discussed searching for motifs in large
genomes, in which random occurrences of the motif are possible. Our aim is to
quantify just how frequently random motifs occur.
One class of motifs of interest are promoters, or regions of DNA that initiate the transcription of a
gene. A promoter is usually located shortly before the start of its gene, and it contains specific
intervals of DNA that provide an initial binding site for RNA polymerase to initiate transcription.
Finding a promoter is usually the second step in gene prediction after establishing the presence of
an ORF (see “Open Reading Frames”).
Unfortunately, there is no quick rule for identifying promoters. In Escherichia coli, the promoter
contains two short intervals (TATAAT and TTGACA), which are respectively located 10 and 35 base
pairs upstream from the beginning of the gene's ORF. Yet even these two short intervals are
consensus strings (see “Consensus and Profile”): they represent average-case strings that are not
found intact in most promoters. Bacterial promoters further vary in that some contain additional
intervals used to bind to specific proteins or to change the intensity of transcription.
Eukaryotic promoters are even more difficult to characterize. Most have a TATA box (consensus
sequence: TATAAA), preceded by an interval called a B recognition element, or BRE. These
elements are typically located within 40 bp of the start of transcription. For that matter, eukaryotic
promoters can hold a larger number of additional "regulatory" intervals, which can be found as far as
several thousand base pairs upstream of the gene.
Problem
Our aim in this problem is to determine the probability with which a given motif (a known promoter,
say) occurs in a randomly constructed genome. Unfortunately, finding this probability is tricky;; instead
of forming a long genome, we will form a large collection of smaller random strings having the same
length as the motif;; these smaller strings represent the genome's substrings, which we can then test
against our motif.
Given a probabilistic event , the complement of is the collection of outcomes not belonging
to . Because takes place precisely when does not, we may also call "not ."
For a simple example, if is the event that a rolled die is 2 or 4, then . is the event
that the die is 1, 3, 5, or 6, and . In general, for any event we will have the identity that
.
Given: A positive integer , a number between 0 and 1, and a DNA string of
length at most 10 bp.
Return: The probability that if random DNA strings having the same length as are constructed
with GC-content (see “Introduction to Random Strings”), then at least one of the strings equals .
We allow for the same random string to be created more than once.
Sample Dataset
90000 0.6
ATAGCCGA
Sample Output
0.689
Problem 50
Counting Subsets
Characters and SNPs
A character is any feature (genetic, physical, etc.) that divides a collection of
organisms into two separate groups. One commonly used genetic character is
the possession of a single-nucleotide polymorphism, or SNP.
In a process called genotyping, the SNP markers taken from a large number of human donors
have been used very successfully to catalogue the migration and differentiation of human
populations over the last 200,000 years. For $199, you can participate in National Geographic's
Genographic Project, and discover your own genetic heritage.
Whether we use genetic or physical characters, we may think of a collection of characters as a
collection of "ON"/"OFF" switches. An organism is said to possess a character in the "ON"
position (although often the assignment of "ON"/"OFF" is arbitrary). Given a collection of taxa, we
may represent a character by the collection of taxa possessing the character.
Problem
A set is the mathematical term for a loose collection of objects, called elements. Examples of sets
include and , the set containing all real numbers. We
even have the empty set, represented by or , which contains no elements at all. Two sets are
equal when they contain the same elements. In other words, in contrast to permutations, the ordering
of the elements of a set is unimportant (e.g., is equivalent
to ). Sets are not allowed to contain duplicate elements,
so that is not a set. We have already used sets of 2
elements to represent edges from a graph.
A set is a subset of if every element of is also an element of , and we write . For
example, , and is a subset
of every set (including itself!).
As illustrated in the biological introduction, we can use subsets to represent the collection of taxa
possessing a character. However, the number of applications is endless;; for example, an event in
probability can now be defined as a subset of the set containing all possible outcomes.
Our first question is to count the total number of possible subsets of a given set.
Return: The total number of subsets of modulo 1,000,000.
Sample Dataset
Sample Output
Hint
What does counting subsets have to do with characters and "ON"/"OFF" switches?
Problem 51
Introduction to Alternative Splicing
The Baby and the Bathwater
In “RNA Splicing”, we described the

process by which the exons are spliced
out from a molecule of pre-mRNA and
reassembled to yield a final mRNA for the
purposes of protein translation.
However, the chaining of exons does not always proceed in
the same manner;; alternative splicing describes the fact
that all the exons from a gene are not necessarily joined
together in order to produce an mRNA. The most common Figure 1. Alternative splicing induces
form of alternative splicing is exon skipping, in which different protein isoforms.
certain exons are omitted along with introns.
Alternative splicing serves a vital evolutionary purpose, as it greatly increases the number of
different proteins that can be translated from a given gene;; different proteins produced from the
same gene as a result of alternative splicing are called protein isoforms;; see Figure 1 In fact,
about 95% of human genes are commonly spliced in more than one way. At the same time, when
alternative splicing goes wrong, it can create the same negative effects caused by mutations, and it
has been blamed for a number of genetic disorders.
In this problem, we will consider a simplified model of alternative splicing in which any of a
collection of exons can be chained together to create a final molecule of mRNA, under the
condition that we use a minimum number of exons ( ) whose order is fixed. Because the exons
are not allowed to move around, we need only select a subset of at least of our exons to chain
into an mRNA.
The implied computational question is to count the total number of such subsets, which will provide
us with the total possible number of alternatively spliced isoforms for this model.
Problem
In “Counting Subsets”, we saw that the total number of subsets of a set containing elements is
equal to .
However, if we intend to count the total number of subsets of having a fixed size , then we use the
combination statistic , also written .
Given: Positive integers and with .
Return: The sum of combinations for all satisfying , modulo 1,000,000. In
shorthand, .
Sample Dataset
6 3
Sample Output
42
Problem 52
Edit Distance
Point Mutations Include Insertions and Deletions
In “Counting Point Mutations”, we saw that Hamming distance gave us a
preliminary notion of the evolutionary distance between two DNA strings by
counting the minimum number of single nucleotide substitutions that could have
occurred on the evolutionary path between the two strands.
However, in practice, homologous strands of DNA or protein are rarely the same length because
point mutations also include the insertion or deletion of a single nucleotide (and single amino acids
can be inserted or deleted from peptides). Thus, we need to incorporate these insertions and
deletions into the calculation of the minimum number of point mutations between two strings. One
of the simplest models charges a unit "cost" to any single-symbol insertion/deletion, then (in
keeping with parsimony) requests the minimum cost over all transformations of one genetic string
into another by point substitutions, insertions, and deletions.
Problem
Given two strings and (of possibly different lengths), the edit distance is the minimum
number of edit operations needed to transform into , where an edit operation is defined as the
substitution, insertion, or deletion of a single symbol.
The latter two operations incorporate the case in which a contiguous interval is inserted into or deleted
from a string;; such an interval is called a gap. For the purposes of this problem, the insertion or
deletion of a gap of length still counts as distinct edit operations.
Given: Two protein strings and in FASTA format (each of length at most 1000 aa).
Return: The edit distance .
Sample Dataset
>Rosalind_39
PLEASANTLY
>Rosalind_11
MEANLY
Sample Output
5
Problem 53
Expected Number of Restriction Sites
A Shot in the Dark
In “Locating Restriction Sites”, we first familiarized ourselves with restriction

enzymes. Recall that these enzymes are used by bacteria to cut through both
strands of viral DNA, thus disarming the virus: the viral DNA locations where these
cuts are made are known as restriction sites. Recall also that every restriction
enzyme is preprogrammed with a reverse palindromic interval of DNA to which it will bind and cut,
called a recognition sequence. These even length intervals are usually either 4 or 6 base pairs
long, although longer ones do exist;; rare-cutter enzymes have recognition sequences of 8 or more
base pairs.
In this problem, we will ask a simple question: how does the bacterium "know" that it will probably
succeed in finding a restriction site within the virus's DNA? The answer is that the short length of
recognition sequences guarantees a large number of matches occurring randomly.
Intuitively, we would expect for a recognition sequence of length 6 to occur on average once every
base pairs. Note that this fact does not imply that the associated restriction enzyme
will cut the viral DNA every 4,096 bp;; it may find two restriction sites close together, then not find a
restriction site for many thousand nucleotides.
In this problem, we will generalize the problem of finding an average number of restriction sites to
take into account the GC-content of the underlying string being analyzed.
Problem
Say that you place a number of bets on your favorite sports teams. If their chances of winning are 0.3,
0.8, and 0.6, then you should expect on average to win 0.3 + 0.8 + 0.6 = 1.7 of your bets (of course,
you can never win exactly 1.7!)
More generally, if we have a collection of events , then the expected number of
events occurring is (consult the note following the problem for a
precise explanation of this fact). In this problem, we extend the idea of finding an expected number of
events to finding the expected number of times that a given string occurs as a substring of a random
string.
Given: A positive integer ( ), a DNA string of even length at most 10, and an
array of length at most 20, containing numbers between 0 and 1.
Return: An array having the same length as in which represents the expected number of
times that will appear as a substring of a random DNA string of length , where is formed with
GC-content (see “Introduction to Random Strings”).
Sample Dataset
10
AG
0.25 0.5 0.75
Sample Output
0.422 0.563 0.422
The Mathematical Details
In this problem, we are speaking of an expected number of events;; how can we tie this into the
definition of expected value that we already have from “Calculating Expected Offspring”?
The answer relies on a slick mathematical trick. For any event , we can form a random variable
for , called an indicator random variable . For an outcome , when belongs
to and when belongs to .
For an indicator random variable , verify that .
You should also verify from our original formula for expected value that for any two random variables
and , is equal to . As a result, the expected number of events
occurring, or , reduces to
.
Problem 54
Motzkin Numbers and RNA Secondary Structures
Dull, Unhappy People
In “Catalan Numbers and RNA Secondary Structures”, we talked about counting
the number of ways for an even number of people to shake hands at a party
without crossing hands. However, in the real world, parties only contain an even
number of people about 40% of the time, and mathematicians don't enjoy
socializing. So we should instead count the total number of ways for some of the people at the
party to shake hands without crossing.
In the biological world, people are far more social, but not every nucleotide in a strand of RNA winds
up base pairing with another nucleotide during RNA folding. As a result, we want to loosen this
assumption and count the total number of different secondary structures of an RNA strand whose
base pairs don't overlap (i.e., we still forbid pseudoknots in the strand).
Problem
Similarly to our definition of the Catalan numbers, the -th Motzkin number counts the number
of ways to form a (not necessarily perfect) noncrossing matching in the complete graph
containing nodes. For example, Figure 1 demonstrates that . Note in this figure that
technically, the "trivial" matching that contains no edges at all is considered to be a matching,
because it satisfies the defining condition that no two edges
are incident to the same node.
How should we compute the Motzkin numbers? As with

Catalan numbers, we will take . To calculate
in general, assume that the nodes of are labeled
around the outside of a circle with the integers between 1 and Figure 1. The 21 distinct ways to
form a noncrossing matching on 5
, and consider node 1, which may or may not be involved in labeled nodes.
a matching. If node 1 is not involved in a matching, then there
are ways of matching the remaining nodes. If
node 1 is involved in a matching, then say it is matched to
node : this leaves nodes on one side of edge
and nodes on the other side;; as with the Catalan
numbers, no edge can connect the two sides, which gives us
ways of matching the remaining edges.
Allowing to vary between and yields the following Figure 2. Two possible noncrossing
matchings of basepair edges in the
recurrence relation for the Motzkin numbers: bonding graph corresponding to
. RNA string UAGCGUGAUCAC.
To count all possible secondary structures of a given RNA

string that do not contain pseudoknots, we need to modify the Motzkin recurrence so that it counts
only matchings of basepair edges in the bonding graph corresponding to the RNA string;; see Figure 2
Given: An RNA string of length at most 300 bp.
Return: The total number of noncrossing matchings of basepair edges in the bonding graph of ,
modulo 1,000,000.
Sample Dataset
>Rosalind_57
AUAU
Sample Output
Problem 55
Distances in Trees
Paths in Trees
For any two nodes of a tree, a unique path connects the nodes;; more specifically,
there is a unique path connecting any pair of leaves. Why must this be the case?
If more than one path connected two nodes, then they would necessarily form a
cycle, which would violate the definition of tree.
The uniqueness of paths connecting nodes in a tree is helpful in phylogenetic analysis because a
rudimentary measure of the separation between two taxa is the distance between them in the tree,
which is equal to the number of edges on the unique path connecting the two leaves corresponding
to the taxa.
Problem
Newick format is a way of representing trees even more

concisely than using an adjacency list, especially when
dealing with trees whose internal nodes have not been labeled.
First, consider the case of a rooted tree . A collection of

leaves of are neighbors if they are all
adjacent to some internal node . Newick format for is
obtained by iterating the following key step: delete all the
edges from and label with .
This process is repeated all the way to the root, at which point
a semicolon signals the end of the tree.
A number of variations of Newick format exist. First, if a node
is not labeled in , then we simply leave blank the space Figure 1. This tree can be
represented in Newick format in a
occupied by the node. In the key step, we can write number of ways, including (C, D, (A,
in place of if the are B));; (A, (D, C), B);; and (((A, B), C))D;;.
labeled;; if none of the nodes are labeled, we can write
.
A second variation of Newick format occurs when is unrooted, in which case we simply select any
internal node to serve as the root of . A particularly peculiar case of Newick format arises when we
choose a leaf to serve as the root.
Note that there will be a large number of different ways to represent in Newick format;; see Figure 1.
Given: A collection of trees ( ) in Newick format, with each tree containing at most 200
nodes;; each tree is followed by a pair of nodes and in .
Return: A collection of positive integers, for which the th integer represents the distance
between and in .
Sample Dataset
(cat)dog;
dog cat
(dog,cat);
dog cat
Sample Output
1 2
Problem 56
Interleaving Two Motifs
Two Motifs, One Gene
Recall that in “Finding a Shared Spliced Motif”, we found the longest motif that
could have been shared by two genetic strings, allowing for the motif to be split
onto multiple exons in the process. As a result, we needed to find a longest
common subsequence of the two strings (which extended the problem of finding a
longest common substring from “Finding a Shared Motif”).
In this problem, we consider an inverse problem of sorts in which we are given two different motifs
and we wish to interleave them together in such a way as to produce a shortest possible genetic
string in which both motifs occur as subsequences.
Problem
A string is a supersequence of another string if contains as a subsequence.
A common supersequence of strings and is a string that serves as a supersequence of both
and . For example, "GACCTAGGAACTC" serves as a common supersequence of "ACGTC" and
"ATAT". A shortest common supersequence of and is a supersequence for which there does not
exist a shorter common supersequence. Continuing our example, "ACGTACT" is a shortest common
supersequence of "ACGTC" and "ATAT".
Given: Two DNA strings and .

Return: A shortest common supersequence of and . If multiple solutions exist, you may output
any one.
Sample Dataset
ATCTGAT
TGCATA
Sample Output
ATGCATGAT
Problem 57
Sorting by Reversals
Reconstructing Evolutionary Histories
When we calculate the Hamming distance between two genetic strings, we can
easily infer a collection of point mutations that occurred on the evolutionary path
between the two strings by simply examining the mismatched symbols. However,
when calculating the reversal distance (see “Reversal Distance”), we only have the
minimum number of reversals separating two permutations.
The computational problem of sorting by reversals demands instead that we provide a minimum
list of reversals transforming one permutation into another. As a result, sorting by reversals
subsumes the calculation of reversal distance: once we have a minimum collection of reversals, the
reversal distance follows immediately.
Problem
A reversal of a permutation can be encoded by the two indices at the endpoints of the interval that it
inverts;; for example, the reversal that transforms into is encoded by
.
A collection of reversals sorts into if the collection contains reversals, which when
successively applied to yield .
Given: Two permutations and , each of length 10.

Return: The reversal distance , followed by a collection of reversals sorting into . If
multiple collections of such reversals exist, you may return any one.
Sample Dataset
1 2 3 4 5 6 7 8 9 10
1 8 9 3 2 7 6 5 4 10
Sample Output
2
4 9
2 5
Problem 58
Inferring Protein from Spectrum
Introduction to Mass Spectrometry

In “Calculating Protein Mass”, we briefly mentioned an analytic chemical method
called mass spectrometry, which aims to measure the mass-to-charge ratio of a
particle or a molecule. In a mass spectrometer, a sample is vaporized (turned into
gas), and then particles from the sample are ionized. The resulting ions are
placed into an electromagnetic field, which separates them based on their charge
and mass. The output of the mass spectrometer is a mass spectrum, or a plot of
ions' possible mass-to-charge ratio values with the intensity (actual observed
frequency) of ions having these mass-to-charge values.
For the moment, we will ignore charge and consider a list of the ions' monoisotopic masses as a
simplified spectrum. Researchers do not possess cheap technology to go in and examine a
protein one amino acid at a time (molecules are too submicroscopic). Instead, to determine a
protein's structure, we will split several copies of the protein into smaller pieces, then weigh the
resulting fragments. To do this, we assume that each cut (breakage point) occurs between two
amino acids and that we can measure the mass of the resulting pieces for all possible cuts.
For example, the (unknown) protein "PRTEIN" can be cut in five possible ways: "P" and "RTEIN";;
"PR" and "TEIN";; "PRT" and "EIN";; "PRTE" and "IN";; "PRTEI" and "N". We then can measure the
masses of all fragments, including the entire string. The "left" end of a protein is called its N-
terminus, and the ions corresponding to the protein string's prefixes (P, PR, PRT, PRTE, PRTEI)
are called b-ions. The "right" end of the protein is called its C-terminus, and the ions
corresponding to the string's suffixes (N, IN, EIN, TEIN, RTEIN) are called y-ions. The difference in
the masses of two adjacent b-ions (or y-ions) gives the mass of one amino acid residue;; for
example, the difference between the masses of "PRT" and "PR" must be the mass of "T." By
extension, knowing the masses of every b-ion of a protein allows us to deduce the protein's
identity.
Problem
The prefix spectrum of a weighted string is the collection of all its prefix weights.
Given: A list of ( ) positive real numbers.
Return: A protein string of length whose prefix spectrum is equal to (if multiple solutions
exist, you may output any one of them). Consult the monoisotopic mass table.
Sample Dataset
3524.8542
3710.9335
3841.974
3970.0326
4057.0646
Sample Output
WMQS
Problem 59
Introduction to Pattern Matching
If At First You Don't Succeed...
We introduced the problem of finding a motif in a genetic string in “Finding a Motif
in DNA”. More commonly, we will have a collection of motifs that we may wish to
find in a larger string, for example when searching a genome for a collection of
known genes.
This application sets up the algorithmic problem of pattern matching, in which we are searching a
large string (called a text) for instances of a collection of smaller strings, called patterns. For the
moment, we will focus on requiring that all matches should be exact.
The most obvious method for finding exact patterns in a text is to simply apply a simple "sliding
window" algorithm for each pattern. However, this method is time-consuming if we have a large
number of patterns to consider (which will often be the case when dealing with a database of
genes). It would be better if instead of traversing the genome for every pattern, we could somehow
only traverse it once. To this end, we will need a data structure that can efficiently organize a
collection of patterns.
Problem
Given a collection of strings, their trie (often pronounced "try"

to avoid ambiguity with the general term tree) is a rooted tree
formed as follows. For every unique first symbol in the strings,
an edge is formed connecting the root to a new vertex. This
symbol is then used to label the edge.
We may then iterate the process by moving down one level as
follows. Say that an edge connecting the root to a node is
labeled with 'A';; then we delete the first symbol from every
string in the collection beginning with 'A' and then treat as
our root. We apply this process to all nodes that are adjacent
to the root, and then we move down another level and
continue. See Figure 1 for an example of a trie. Figure 1. The trie corresponding to
the strings 'apple', 'apropos',
As a result of this method of construction, the symbols along 'banana', 'bandana', and 'orange'.
the edges of any path in the trie from the root to a leaf will Each path from root to leaf encodes
spell out a unique string from the collection, as long as no one of these strings.
string is a prefix of another in the collection (this would cause
the first string to be encoded as a path terminating at an internal node).
Given: A list of at most 100 DNA strings of length at most 100 bp, none of which is a prefix of
another.
Return: The adjacency list corresponding to the trie for these patterns, in the following format. If
has nodes, first label the root with 1 and then label the remaining nodes with the integers 2
through in any order you like. Each edge of the adjacency list of will be encoded by a triple
containing the integer representing the edge's parent node, followed by the integer representing the
edge's child node, and finally the symbol labeling the edge.
Sample Dataset
ATAGA
ATC
GAT
Sample Output
1 2 A
2 3 T
3 4 A
4 5 G
5 6 A
3 7 C
1 8 G
8 9 A
9 10 T
Problem 60
Comparing Spectra with the Spectral Convolution
Comparing Spectra
Suppose you have two mass spectra, and you want to check if they both were
obtained from the same protein;; you will need some notion of spectra similarity.
The simplest possible metric would be to count the number of peaks in the mass
spectrum that the spectra share, called the shared peaks count;; its analogue for
simplified spectra is the number of masses that the two spectra have in common.
The shared peaks count can be useful in the simplest cases, but it does not help us if, for
example, one spectrum corresponds to a peptide contained inside of another peptide from which
the second spectrum was obtained. In this case, the two spectra are very similar, but the shared
peaks count will be very small. However, if we shift one spectrum to the right or left, then shared
peaks will align. In the case of simplified spectra, this means that there is some shift value such
that adding to the weight of every element in one spectrum should create a large number of
matches in the other spectrum.
Problem
A multiset is a generalization of the notion of set to include a collection of objects in which each
object may occur more than once (the order in which objects are given is still unimportant). For a
multiset , the multiplicity of an element is the number of times that occurs in the set;; this
multiplicity is denoted . Note that every set is included in the definition of multiset.
The Minkowski sum of multisets and containing real numbers is the new multiset
formed by taking all possible sums of an element from and an element from .
The Minkowski sum could be defined more concisely as
, The Minkowski difference is defined
analogously by taking all possible differences .
If and represent simplified spectra taken from two peptides, then is called the
spectral convolution of and . In this notation, the shared peaks count is represented by
, and the value of for which has the maximal value is the shift value
maximizing the number of shared masses of and .
Given: Two multisets of positive real numbers and . The size of each multiset is at most
200.
Return: The largest multiplicity of , as well as the absolute value of the number
maximizing (you may return any such value if multiple solutions exist).
Sample Dataset
186.07931 287.12699 548.20532 580.18077 681.22845 706.27446 782.27613 9

68.35544 968.35544
101.04768 158.06914 202.09536 318.09979 419.14747 463.17369
Sample Output
3
85.03163
Note
Observe that is equivalent to , but it is not usually the case that is the
same as ;; in this case, one multiset can be obtained from the other by negating every
element.
Problem 61
Creating a Character Table
Introduction to Character-Based Phylogeny
Before the modern genetics revolution, phylogenies were constructed from

physical characters resulting from direct structural comparison of taxa. A great
deal of analysis relied on the fossil record, as fossils provided the only concrete
framework for studying the appearance of extinct species and for inferring how
they could have evolved into present-day organisms.
A classic case illustrating the utility of the fossil record is the case of dinosaur pelvic bones. In
1887, Harry Seeley proposed a new classification of dinosaurs into two orders, Saurischia and
Ornithischia: the former possessed hip bones shaped like those found in reptiles, whereas the
latter had a much different hip shape that resembled birds. Seeley's pelvic classification has
survived to the present day as the principal division of dinosaurs.
The key point is that hip bone shape is a physical character that separates all dinosaurs into two
different groups. Our hope is to construct a phylogeny solely from a collection of characters.
Throughout character-based phylogeny, our two-part assumption is that all taxa possessing a
character must have evolved from a single ancestor that introduced this character, and conversely,
any taxon not possessing the character cannot be descended from this ancestor.
Problem
Given a collection of taxa, any subset of these taxa can be seen as encoding a character that
divides the taxa into the sets and ;; we can represent the character by , which is called a
split. Alternately, the character can be represented by a character array of length for which
if the th taxon belongs to and if the th taxon belongs to (recall the
"ON"/"OFF" analogy from “Counting Subsets”).
At the same time, observe that the removal of an edge from an unrooted binary tree produces two
separate trees, each one containing a subset of the original taxa. So each edge may also be encoded
by a split .
A trivial character isolates a single taxon into a group of its own. The corresponding split
must be such that or contains only one element;; the edge encoded by this split must be
incident to a leaf of the unrooted binary tree, and the array for the character contains exactly one 0 or
exactly one 1. Trivial characters are of no phylogenetic interest because they fail to provide us with
information regarding the relationships of taxa to each other. All other characters are called nontrivial
characters (and the associated splits are called nontrivial splits).
A character table is a matrix in which each row represents the array notation for a nontrivial
character. That is, entry denotes the "ON"/"OFF" position of the th character with respect to the
th taxon.
Given: An unrooted binary tree in Newick format for at most 200 species taxa.
Return: A character table having the same splits as the edge splits of . The columns of the
character table should encode the taxa ordered lexicographically;; the rows of the character table may
be given in any order. Also, for any given character, the particular subset of taxa to which 1s are
assigned is arbitrary.
Sample Dataset
(dog,((elephant,mouse),robot),cat);
Sample Output
00110
00111
Problem 62
Constructing a De Bruijn Graph
Wading Through the Reads
Because we use multiple copies of the genome to generate and identify reads for
the purposes of fragment assembly, the total length of all reads will be much
longer than the genome itself. This begs the definition of read coverage as the
average number of times that each nucleotide from the genome appears in the
reads. In other words, if the total length of our reads is 30 billion bp for a 3 billion bp genome, then
we have 10x read coverage.
To handle such a large number of -mers for the purposes of sequencing the genome, we need an
efficient and simple structure.
Problem
Consider a set of -mers of some unknown DNA string. Let denote the set containing
all reverse complements of the elements of . (recall from “Counting Subsets” that sets are not
allowed to contain duplicate elements).
The de Bruijn graph of order corresponding to is a digraph defined in the following
way:
Nodes of correspond to all -mers that are present as a substring of a -mer from
.
Edges of are encoded by the -mers of in the following way: for each
-mer in , form a directed edge ( , ).
Given: A collection of up to 1000 DNA strings of equal length (not exceeding 50 bp) corresponding
to a set of -mers.
Return: The adjacency list corresponding to the de Bruijn graph corresponding to .
Sample Dataset
TGAT
CATG
TCAT
ATGC
CATC
CATC
Sample Output
(ATC, TCA)
(ATG, TGA)
(ATG, TGC)
(CAT, ATC)
(CAT, ATG)
(GAT, ATG)
(GCA, CAT)
(TCA, CAT)
(TGA, GAT)
Problem 63
Edit Distance Alignment
Reconstructing Edit Distance
In “Counting Point Mutations”, the calculation of Hamming distance gave us a
clear way to model the sequence of point mutations transforming one genetic
string into another. By simply writing one string directly over the other, we could
count each mismatched symbol as a substitution.
However, in the calculation of edit distance (see “Edit Distance”), the two strings can have different
lengths;; thus, simply superimposing one string over the other does us no good when it comes to
visualizing a sequence of edit operations transforming one string into the other. To remedy this, we
will introduce a new symbol to serve as a placeholder representing an inserted or deleted symbol;;
furthermore, this placeholder will allow us to align two strings of differing lengths.
Problem
An alignment of two strings and is defined by two strings and satisfying the following three
conditions: 1. and must be formed from adding gap symbols "-" to each of and , respectively;;
as a result, and will form subsequences of and . 2. and must have the same length. 3.
Two gap symbols may not be aligned;; that is, if is a gap symbol, then cannot be a gap
symbol, and vice-versa.
We say that and augment and . Writing directly over so that symbols are aligned
provides us with a scenario for transforming into . Mismatched symbols from and correspond to
symbol substitutions;; a gap symbol aligned with a non-gap symbol implies the insertion of
this symbol into ;; a gap symbol aligned with a non-gap symbol implies the deletion of this
symbol from .
Thus, an alignment represents a transformation of into via edit operations. We define the
corresponding edit alignment score of and as (Hamming distance is used because
the gap symbol has been introduced for insertions and deletions). It follows that
, where the minimum is taken over all alignments of and . We call
such a minimum score alignment an optimal alignment (with respect to edit distance).
Given: Two protein strings and in FASTA format (with each string having length at most 1000
aa).
Return: The edit distance followed by two augmented strings and representing an
optimal alignment of and .
Sample Dataset
>Rosalind_43
PRETTY
>Rosalind_97
PRTTEIN
Sample Output
4
PRETTY-‐-‐
PR-‐TTEIN
Problem 64
Inferring Peptide from Full Spectrum
Ions Galore
In “Inferring Protein from Spectrum”, we inferred a protein string from a list of b-
ions. In practice, biologists have no way of distinguishing between b-ions and y-
ions in the simplified spectrum of a peptide. However, we will often possess a pair
of masses in the spectrum corresponding to a single cut. The two corresponding
ions complement each other: for example, mass("PR") + mass("TEIN") = mass("PRTEIN"). As a
result, we can easily infer the mass of a b-ion from its complementary y-ion and vice versa, as long
as we already know the parent mass, i.e., the mass of the entire peptide.
The theoretical simplified spectrum for a protein of length is constructed as follows: form all
possible cuts, then compute the mass of the b-ion and the y-ion at each cut. Duplicate masses are
allowed. You might guess how we could modify “Inferring Protein from Spectrum” to infer a peptide
from its theoretical simplified spectrum;; here we consider a slightly modified form of this problem in
which we attempt to identify the interior region of a peptide given only b-ions and y-ions that are cut
within this region. As a result, we will have constant masses at the beginning and end of the
peptide that will be present in the mass of every b-ion and y-ion, respectively.
Problem
Say that we have a string containing as an internal substring, so that there exist nonempty
substrings and of such that can be written as . A t-prefix contains all of and none
of ;; likewise, a t-suffix contains all of and none of .
Given: A list containing positive real numbers ( ). The first number in is the
parent mass of a peptide , and all other numbers represent the masses of some b-ions and y-ions of
(in no particular order). You may assume that if the mass of a b-ion is present, then so is that of its
complementary y-ion, and vice-versa.
Return: A protein string of length for which there exist two positive real numbers and
such that for every prefix and suffix of , each of and is equal to an
element of . (In other words, there exists a protein string whose -prefix and -suffix weights
correspond to the non-parent mass values of .) If multiple solutions exist, you may output any one.
Sample Dataset
1988.21104821
610.391039105
738.485999105
766.492149105
863.544909105
867.528589105
992.587499105
995.623549105
1120.6824591
1124.6661391
1221.7188991
1249.7250491
1377.8200091
Sample Output
KEKEP
Problem 65
Independent Segregation of Chromosomes
Mendel's Work Examined
Mendel's laws of heredity were initially ignored, as only 11 papers have been
found that cite his paper between its publication in 1865 and 1900. One reason for
Mendel's lack of popularity is that information did not move quite so readily as in
the modern age;; perhaps another reason is that as a friar in an Austrian abbey,
Mendel was already isolated from Europe's university community.
It is fair to say that no one who did initially read Mendel's work fully believed that traits for more
complex organisms, like humans, could be broken down into discrete units of heredity (i.e.,
Mendel's factors). This skepticism was well-founded in empirical studies of inheritance, which
indicated a far more complex picture of heredity than Mendel's theory dictated. The friar himself
admitted that representing every trait with a single factor was overly simplistic, and so he proposed
that some traits are polymorphic, or encoded by multiple different factors.
Yet any hereditary model would ultimately be lacking without an understanding of how traits are
physically passed from organisms to their offspring. This physical mechanism was facilitated by
Walther Flemming's 1879 discovery of chromosomes in salamander eggs during cell division,
followed by Theodor Boveri's observation that sea urchin embryos with chromatin removed failed to
develop correctly (implying that traits must somehow be encoded on chromosomes). By the turn of
the 20th century, Mendel's work had been rediscovered by Hugo de Vries and Carl Correns, but it
was still unclear how Mendel's hereditary model could be tied to chromosomes.
Fortunately, Walter Sutton demonstrated that grasshopper chromosomes occur in matched pairs
called homologous chromosomes, or homologs. We now know that the DNA found on
homologous chromosomes is identical except for minor variations attributable to SNPs and small
rearrangements, which are typically insertions and deletions. Sutton himself, working five decades
before Watson & Crick and possessing no real understanding of DNA, actually surmised that
variations to homologous chromosomes should somehow correspond to Mendel's alleles.
Yet it still remained to show how chromosomes themselves are inherited. Most multicellular
organisms are diploid, meaning that their cells possess two sets of chromosomes;; humans are
included among diploid organisms, having 23 homologous chromosome pairs.
Gametes (i.e., sex cells) in diploid organisms form an exception and are haploid, meaning that
they only possess one chromosome from each pair of homologs. During the fusion of two gametes
of opposite sex, a diploid embryo is formed by simply uniting the two gametes' halved chromosome
sets.
Mendel's first law can now be explained by the fact that during the meiosis each gamete randomly
selects one of the two available alleles of the particular gene.
Mendel's second law follows from the fact that gametes select nonhomologous chromosomes
independently of each other;; however, this law will hold only for factors encoded on nonhomologous
chromosomes, which leaves open the inheritance of factors encoded on homologous
chromosomes.
Problem
Consider a collection of coin flips. One of the most natural questions we can ask is if we flip a coin 92
times, what is the probability of obtaining 51 "heads", vs. 27 "heads", vs. 92 "heads"?
Each coin flip can be modeled by a uniform random variable in which each of the two outcomes
("heads" and "tails") has probability equal to 1/2. We may assume that these random variables are
independent (see “Independent Alleles”);; in layman's terms, the outcomes of the two coin flips do not
influence each other.
A binomial random variable takes a value of if consecutive "coin flips" result in total
"heads" and total "tails." We write that .
Return: An array of length in which represents the common logarithm of the probability
that two diploid siblings share at least of their chromosomes (we do not consider recombination
for now).
Sample Dataset
Sample Output
0.000 -‐0.004 -‐0.024 -‐0.082 -‐0.206 -‐0.424 -‐0.765 -‐1.262 -‐1.969 -‐3.010
Problem 66
Finding Disjoint Motifs in a Gene
Disjoint Motifs
In this problem, we will consider an algorithmic (but not particularly practical)
variant of motif finding for multiple motifs. Say we have two motifs corresponding
to the coding regions of genes, and we want to know whether these motifs can be
found in genes occupying the same region of the genome. To prevent exons from
coinciding, we further stipulate that the two motifs are nonoverlapping.
In this problem, we will ask whether two disjoint motifs can be located in a given string. We
considered a similar problem in “Interleaving Two Motifs”, which asked us to find a shortest possible
string containing two motifs;; however, in that problem, the motifs were allowed to coincide.
Problem
Given three strings , , and , we say that and can be interwoven into if there is some
substring of made up of and as disjoint subsequences.
For example, the strings " " and " " can be interwoven into " ".
However, they cannot be interwoven into " " because of the appearance of
the four 'A's in the middle of the subsequences. Similarly, even though both " " is a shortest
common supersequence of and , it is not possible to interweave these two strings into
" " because the two desired subsequences must be disjoint;; see “Interleaving Two Motifs” for
details on finding a shortest common supersequence of two strings.
Given: A text DNA string of length at most 10 kbp, followed by a collection of ( ) DNA
strings of length at most 10 bp acting as patterns.
Return: An matrix for which if the th and th pattern strings can be
interwoven into and otherwise.
Sample Dataset
GACCACGGTT
ACAG
GT
CCG
Sample Output
0 0 1
0 1 0
1 0 0
Citation
This problem follows Jones & Pevzner, An Introduction to Bioinformatics Algorithms, Problem 6.31
Problem 67
Finding the Longest Multiple Repeat
Long Repeats
We saw in “Introduction to Pattern Matching” that a data structure commonly
used to encode the relationships among a collection of strings was the trie, which
is particularly useful when the strings represent a collection of patterns that we
wish to match to a larger text.
The trie is helpful when processing multiple strings at once, but when we want to analyze a single
string, we need something different.
In this problem, we will use a new data structure to handle the problem of finding long repeats in the
genome. Recall from “Finding a Motif in DNA” that cataloguing these repeats is a problem of the
utmost interest to molecular biologists, as a natural correlation exists between the frequency of a
repeat and its influence on RNA transcription. Our aim is therefore to identify long repeats that
occur more than some predetermined number of times.
Problem
A repeated substring of a string of length is simply a

substring that appears in more than one location of ;; more
specifically, a k-fold substring appears in at least k distinct
locations.
The suffix tree of , denoted , is defined as follows:

Figure 1. The suffix tree for s =
is a rooted tree having exactly leaves. GTCCGAAGCTCCGG. Note that the
Every edge of is labeled with a substring of , dollar sign has been appended to a
where is the string formed by adding a placeholder substring of the tree to mark the end
of s. Every path from the root to a leaf
symbol $ to the end of . corresponds to a unique suffix of
Every internal node of other than the root has at GTCCGAAGCTCCGG, and each leaf
is labeled with the location in s of
least two children;; i.e., it has degree at least 3. the suffix ending at that leaf.
The substring labels for the edges leading from a node to
its children must begin with different symbols.
By concatenating the substrings along edges, each path from the root to a leaf corresponds to a
unique suffix of .
See Figure 1 for an example of a suffix tree.
Given: A DNA string (of length at most 20 kbp) with $ appended, a positive integer , and a list
of edges defining the suffix tree of . Each edge is represented by four components:
1. the label of its parent node in ;;

2. the label of its child node in ;;
3. the location of the substring of assigned to the edge;; and
4. the length of .
Return: The longest substring of that occurs at least times in . (If multiple solutions exist, you
may return any single solution.)
Sample Dataset
CATACATAC$
2
node1 node2 1 1
node1 node7 2 1
node1 node14 3 3
node1 node17 10 1
node2 node3 2 4
node2 node6 10 1
node3 node4 6 5
node3 node5 10 1
node7 node8 3 3
node7 node11 5 1
node8 node9 6 5
node8 node10 10 1
node11 node12 6 5
node11 node13 10 1
node14 node15 6 5
node14 node16 10 1
Sample Output
CATAC
Hint
How can repeated substrings of be located in ?
Problem 68
Newick Format with Edge Weights
Weighting the Tree
A vital goal of creating phylogenies is to quantify a molecular clock that indicates the amount of
evolutionary time separating two members of the phylogeny. To this end, we will assign numbers to
the edges of a tree so that the number assigned to an edge represents the amount of time
separating the two species at each end of the edge. More generally, the
evolutionary time between any two species will be given by simply adding the
individual times connecting the nodes.
Problem
In a weighted tree, each edge is assigned a (usually positive) number, called its weight. The
distance between two nodes in a weighted tree becomes the sum of the weights along the unique path
connecting the nodes.
To generalize Newick format to the case of a weighted tree , during our repeated "key step," if leaves
are neighbors in , and all these leaves are incident to , then we replace with
, where is now the weight on the edge .
Given: A collection of weighted trees ( ) in Newick format, with each tree containing at
most 200 nodes;; each tree is followed by a pair of nodes and in .
Return: A collection of numbers, for which the th number represents the distance between
and in .
Sample Dataset
(dog:42,cat:33);
cat dog
((dog:4,cat:3):74,robot:98,elephant:58);
dog elephant
Sample Output
75 136
Problem 69
Wobble Bonding and RNA Secondary Structures
Don't Look Down
We have discussed the problem of counting RNA secondary structures in
previous problems. In this problem, we will add some assumptions to those used
in “Motzkin Numbers and RNA Secondary Structures” to provide ourselves with an
ultimately robust way of counting feasible RNA secondary structures.
First, in addition to the classic Watson and Crick base pairing of adenine with uracil and cytosine
with guanine, uracil sometimes bonds with guanine, forming what is called a wobble base pair.
As a result, we would like to allow wobble base pairing.
Second, although RNA folds over itself during base pairing, the structure of the molecule is rigid
enough to prevent bases located very close to each other on the strand from bonding to each other.
Problem
Given an RNA string , we will augment the bonding graph of
by adding basepair edges connecting all occurrences of 'U'
to all occurrences of 'G' in order to represent possible wobble
base pairs.
We say that a matching in the bonding graph for is valid if it
is noncrossing (to prevent pseudoknots) and has the property
that a basepair edge in the matching cannot connect symbols
Figure 1. A valid matching of
and unless (to prevent nearby nucleotides basepair edges in the bonding
from base pairing). graph of an RNA string, followed by
a diagram of how this bonding will
See Figure 1 for an example of a valid matching if we allow induce the resulting folded RNA.
wobble base pairs. In this problem, we will wish to count all
possible valid matchings in a given bonding graph;; see Figure
2 for all possible valid matchings in a small bonding graph,
assuming that we allow wobble base pairing.
Given: An RNA string (of length at most 200 bp).
Return: The total number of distinct valid matchings of
basepair edges in the bonding graph of . Assume that
wobble base pairing is allowed.
Figure 2. All 12 possible valid
basepair matchings in the bonding
Sample Dataset graph corresponding to the string s
= CGAUGCUAG (including the trivial
matching in which no edges are
AUGCUAGUACGGAGCGAGUCUAGCGAGCGAUGUCGUGAGUAC matched.) Courtesy Brian Tjaden.
UAUAUAUGCGCAUAAGCCACGU
Sample Output
284850219977421
Problem 70
Counting Disease Carriers
Genetic Drift and the Hardy-Weinberg Principle
Mendel's laws of segration and independent assortment are excellent for the
study of individual organisms and their progeny, but they say nothing about how
alleles move through a population over time. Our first question is: when can we
assume that the ratio of an allele in a population, called the allele frequency, is
stable?
G. H. Hardy and Wilhelm Weinberg independently considered this question at the turn of the 20th
Century, shortly after Mendel's ideas had been rediscovered. They concluded that the percentage of
an allele in a population of individuals is in genetic equilibrium when five conditions are satisfied:
1. The population is so large that random changes in the allele frequency are negligible.
2. No new mutations are affecting the gene of interest;;
3. The gene does not influence survival or reproduction, so that natural selection is not occurring;;
4. Gene flow, or the change in allele frequency due to migration into and out of the population, is
negligible.
5. Mating occurs randomly with respect to the gene of interest.
The Hardy-Weinberg principle states that if a population is in genetic equilibrium for a given
allele, then its frequency will remain constant and evenly distributed through the population. Unless
the gene in question is important to survival or reproduction, Hardy-Weinberg usually offers a
reasonable enough model of population genetics.
One of the many benefits of the Mendelian theory of inheritance and simplifying models like Hardy-
Weinberg is that they help us predict the probability with which genetic diseases will be inherited,
so as to take appropriate preventative measures. Genetic diseases are usually caused by
mutations to chromosomes, which are passed on to subsequent generations.
The simplest and most widespread case of a genetic disease is a single gene disorder, which is
caused by a single mutated gene. Over 4,000 such human diseases have been identified, including
cystic fibrosis and sickle-cell anemia. In both of these cases, the individual must possess two
recessive alleles for a gene in order to contract the disease. Thus, carriers can live their entire lives
without knowing that they can pass the disease on to their children.
The above introduction to genetic equilibrium leaves us with a basic and yet very practical question
regarding gene disorders: if we know the number of people who have a disease encoded by a
recessive allele, can we predict the number of carriers in the population?
Problem
To model the Hardy-Weinberg principle, assume that we have a population of diploid individuals. If
an allele is in genetic equilibrium, then because mating is random, we may view the
chromosomes as receiving their alleles uniformly. In other words, if there are dominant alleles, then
the probability of a selected chromosome exhibiting the dominant allele is simply .
Because the first assumption of genetic equilibrium states that the population is so large as to be
ignored, we will assume that is infinite, so that we only need to concern ourselves with the value of
.
Given: An array for which represents the proportion of homozygous recessive individuals for
the -th Mendelian factor in a diploid population. Assume that the population is in genetic equilibrium
for all factors.
Return: An array having the same length as in which represents the probability that a
randomly selected individual carries at least one copy of the recessive allele for the -th factor.
Sample Dataset
0.1 0.25 0.5

Sample Output
0.532 0.75 0.914
Problem 71
Creating a Character Table from Genetic Strings
Phylogeny from Genetic Characters
In “Creating a Character Table”, we introduced the character table as a way of
representing a number of characters simultaneously. In that problem, we found a
character table representing an unrooted binary tree on a collection of taxa.
Of course, in practice, the problem operates in reverse. We first need to generate a character table
before we can model a phylogeny on this table. In modern genetics, a reliable way to obtain a large
number of characters is by using SNPs. As mentioned in “Counting Subsets”, for a given SNP, we
can divide taxa into two sets depending on which of two bases is present at the nucleotide, thus
defining the split of a character.
Problem
A collection of strings is characterizable if there are at most two possible choices for the symbol at
each position of the strings.
Given: A collection of at most 100 characterizable DNA strings, each of length at most 300 bp.
Return: A character table for which each nontrivial character encodes the symbol choice at a single
position of the strings. (Note: the choice of assigning '1' and '0' to the two states of each SNP in the
strings is arbitrary.)
Sample Dataset
ATGCTACC
CGTTTACC
ATTCGACC
AGTCTCCC
CGTCTATC
Sample Output
10110
10100
Note
Recall that the character table does not encode trivial characters.
Problem 72
Counting Optimal Alignments
Beware of Alignment Inference
In “Edit Distance Alignment”, we introduced the concept of an alignment of two
genetic strings having differing lengths with respect to edit distance. This provided
us with a way of visualizing a specific collection of symbol substitutions,
insertions, and deletions that could have taken place on the evolutionary path
between the two strings.
However, simply finding one optimal alignment and declaring that it represents a true evolutionary
history is a dangerous idea because the actual evolutionary picture may be suboptimal. For that
matter, the collection of all optimal alignments may be huge, and the characteristics of these
alignments could differ widely.
In order to begin analyzing the collection of optimal alignments for a pair of strings, the first
question we will ask is simple: just how many optimal alignments exist?
Problem
Recall from “Edit Distance Alignment” that if and are the augmented strings corresponding to an
alignment of strings and , then the edit alignment score of and was given by the Hamming
distance (because and have the same length and already include gap symbols to
denote insertions/deletions).
As a result, we obtain , where the minimum is taken over all
alignments of and . Strings and achieving this minimum correspond to an optimal alignment
with respect to edit alignment score.
Given: Two protein strings and in FASTA format, each of length at most 1000 aa.
Return: The total number of optimal alignments of and with respect to edit alignment score,
modulo 134,217,727 (227-1).
Sample Dataset
>Rosalind_78
PLEASANTLY
>Rosalind_33
MEANLY
Sample Output
Why Are We Counting Modulo 134,217,727?
As a simple example, say that we attempt to count some statistic modulo 10. If computing the
statistic requires us to multiply a collection of integers, and at any point we multiply by a multiple
of 10, then the statistic will automatically become a multiple of 10 and thus congruent to 0 modulo
10. A similar issue can arise when we count a huge number modulo any composite number;;
however, if we count modulo a large prime number (i.e., one without any divisors other than
itself), then problems can only ever arise if when counting our statistic, we multiply by a multiple of
.
Problem 73
Counting Unrooted Binary Trees
Counting Trees
A natural question is to be able to count the total number of distinct unrooted
binary trees having leaves, where each leaf is labeled by some taxon. Before
we can count all these trees, however, we need to have a notion of when two such
trees are the same.
Our tool will be the split. Recall from “Creating a Character Table” that removing any edge from a
tree separates its leaves into sets and , so that each edge of can be labeled by this
split . As a result, an unrooted binary tree can be represented uniquely by its collection of
splits.
Problem
Two unrooted binary trees and having the same labeled leaves are considered to be
equivalent if there is some assignment of labels to the internal nodes of and so that the
adjacency lists of the two trees coincide. As a result, note that and must have the same splits;;
conversely, if the two trees do not have the same splits, then they are considered distinct.
Let denote the total number of distinct unrooted binary trees having labeled leaves.
Return: The value of modulo 1,000,000.
Sample Dataset
5
Sample Output
15
Problem 74
Global Alignment with Scoring Matrix
Generalizing the Alignment Score
The edit alignment score in “Edit Distance Alignment” counted the total number of
edit operations implied by an alignment;; we could equivalently think of this scoring
function as assigning a cost of 1 to each such operation. Another common
scoring function awards matched symbols with 1 and penalizes
substituted/inserted/deleted symbols equally by assigning each one a score of 0, so that the
maximum score of an alignment becomes the length of a longest common subsequence of and
(see “Finding a Shared Spliced Motif”). In general, the alignment score is simply a scoring
function that assigns costs to edit operations encoded by the alignment.
One natural way of adding complexity to alignment scoring functions is by changing the alignment
score based on which symbols are substituted;; many methods have been proposed for doing this.
Another way to do so is to vary the penalty assigned to the insertion or deletion of symbols.
In general, alignment scores can be either maximized or minimized depending on how scores are
established. The general problem of optimizing a particular alignment score is called global
alignment.
Problem
To penalize symbol substitutions differently depending on which two symbols are involved in the
substitution, we obtain a scoring matrix in which represents the (negative) score assigned to
a substitution of the th symbol of our alphabet with the th symbol of .
A gap penalty is the component deducted from alignment score due to the presence of a gap. A gap
penalty may be a function of the length of the gap;; for example, a linear gap penalty is a constant
such that each inserted or deleted symbol is charged ;; as a result, the cost of a gap of length is
equal to .
Return: The maximum alignment score between and . Use:
The BLOSUM62 scoring matrix.
Linear gap penalty equal to 5 (i.e., a cost of -5 is assessed for each gap symbol).
Sample Dataset
>Rosalind_67
PLEASANTLY
>Rosalind_17
MEANLY
Sample Output
Problem 75
Genome Assembly with Perfect Coverage
Cyclic Chromosomes
Recall that although chromosomes taken from eukaryotes have a linear structure,
many bacterial chromosomes are actually circular. We represented a linear
chromosome with a DNA string, so we only need to modify the definition of string
to model circular chromosomes.
Perfect coverage is the phenomenon in fragment assembly of having a read (or -mer) begin at
every possible location in the genome. Unfortunately, perfect coverage is still difficult to achieve, but
fragment assembly technology continues to improve by leaps and bounds, and perfect coverage is
perhaps not the fantasy it once was.
Problem
A circular string is a string that does not have an initial or terminal element;; instead, the string is
viewed as a necklace of symbols. We can represent a circular string as a string enclosed in
parentheses. For example, consider the circular DNA string (ACGTAC), and note that because the
string "wraps around" at the end, this circular string can equally be represented by (CGTACA),
(GTACAC), (TACACG), (ACACGT), and (CACGTA). The definitions of substrings and superstrings are
easy to generalize to the case of circular strings (keeping in mind that substrings are allowed to wrap
around).
Given: A collection of (error-free) DNA -mers ( ) taken from the same strand of a circular
chromosome. In this dataset, all -mers from this strand of the chromosome are present, and their de
Bruijn graph consists of exactly one simple cycle.
Return: A cyclic superstring of minimal length containing the reads (thus corresponding to a
candidate cyclic chromosome).
Sample Dataset
ATTAC
TACAG
GATTA
ACAGA
CAGAT
TTACA
AGATT
Sample Output
GATTACA
Note
The assumption made above that all reads derive from the same strand is practically unrealistic;; in
reality, researchers will not know the strand of DNA from which a given read has been sequenced.
Problem 76
Matching a Spectrum to a Protein
Searching the Protein Database
Many proteins have already been identified for a wide variety of organisms.
Accordingly, there are a large number of protein databases available, and so the
first step after creating a mass spectrum for an unidentified protein is to search
through these databases for a known protein with a highly similar spectrum. In
this manner, many similar proteins found in different species have been identified, which aids
researchers in determining protein function.
In “Comparing Spectra with the Spectral Convolution”, we introduced the spectral convolution and
used it to measure the similarity of simplified spectra. In this problem, we would like to extend this
idea to find the most similar protein in a database to a spectrum taken from an unknown protein.
Our plan is to use the spectral convolution to find the largest possible number of masses that each
database protein shares with our candidate protein after shifting, and then select the database
protein having the largest such number of shared masses.
Problem
The complete spectrum of a weighted string is the multiset containing the weights of every
prefix and suffix of .
Given: A positive integer followed by a collection of protein strings

, , ..., and a
multiset of positive numbers (corresponding to the complete spectrum of some unknown protein
string).
Return: The maximum multiplicity of taken over all strings , followed by the string
for which this maximum multiplicity occurs (you may output any such value if multiple solutions
exist).
Sample Dataset
4
GSDMQS
VWICN
IASWMQS
PVSMGAD
445.17838
115.02694
186.07931
314.13789
317.1198
215.09061
Sample Output
3
IASWMQS
Problem 77
Quartets
Incomplete Characters
The modern revolution in genome sequencing has produced a huge amount of
genetic data for a wide variety of species. One ultimate goal of possessing all this
information is to be able to construct complete phylogenies via direct genome
analysis.
For example, say that we have a gene shared by a number of taxa. We could create a character
based on whether species are known to possess the gene or not, and then use a huge character
table to construct our desired phylogeny. However, the present bottleneck with such a method is
that it assumes that we already possess complete genome information for all possible species.
The race is on to sequence as many species genomes as possible;; for instance, the Genome 10K
Project aims to sequence 10,000 species genomes over the next decade. Yet for the time being,
possessing a complete genomic picture of all Earth's species remains a dream.
As a result of these practical limitations, we need to be able to work with partial characters,
which divide taxa into three separate groups: those possessing the character, those not
possessing the character, and those for which we do not yet have conclusive information.
Problem
A partial split of a set of taxa models a partial character and is denoted by , where and
are still the two disjoint subsets of taxa divided by the character. Unlike in the case of splits, we do
not necessarily require that ;; corresponds to those taxa for which we lack
conclusive evidence regarding the character.
We can assemble a collection of partial characters into a generalized partial character table in
which the symbol is placed in if we do not have conclusive evidence regarding the th taxon
with respect to the th partial character.
A quartet is a partial split in which both and contain precisely two elements. For the
sake of simplicity, we often will consider quartets instead of partial characters. We say that a quartet
is inferred from a partial split if and (or equivalently and
). For example, and can be inferred from .
Given: A partial character table .

Return: The collection of all quartets that can be inferred from the splits corresponding to the
underlying characters of .
Sample Dataset
cat dog elephant ostrich mouse rabbit robot

01xxx00
x11xx00
111x00x
Sample Output
{elephant, dog} {rabbit, robot}

{cat, dog} {mouse, rabbit}
{mouse, rabbit} {cat, elephant}
{dog, elephant} {mouse, rabbit}
Problem 78
Using the Spectrum Graph to Infer Peptides
Getting Real with Spectra
In “Inferring Peptide from Full Spectrum”, we considered an idealized version of the
simplified spectrum in which every cut through a given peptide was produced, so
that the spectrum possessed all possible b-ions and y-ions cutting the peptide. In
reality, not every cut will be produced in a spectrum, which may also contain
errors. As a result, it is difficult or impossible to recover an entire peptide from a single spectrum.
In the more practical case of a mass spectrum, where intensity is plotted against ions' mass-
charge ratios, inferring the protein is also greatly complicated by the presence of erratic peaks in
the spectrum.
Problem
For a weighted alphabet and a collection of positive real numbers, the spectrum graph of is
a digraph constructed in the following way. First, create a node for every real number in . Then,
connect a pair of nodes with a directed edge if and is equal to the weight of a
single symbol in . We may then label the edge with this symbol.
In this problem, we say that a weighted string matches if there is some
increasing sequence of positive real numbers in such that
, , ..., and .
Given: A list (of length at most 100) containing positive real numbers.
Return: The longest protein string that matches the spectrum graph of (if multiple solutions
exist, you may output any one of them). Consult the monoisotopic mass table.
Sample Dataset
3524.8542
3623.5245
3710.9335
3841.974
3929.00603
3970.0326
4026.05879
4057.0646
4083.08025
Sample Output
WMSPG
Hint
How can our question be rephrased in terms of the spectrum graph?
Problem 79
Encoding Suffix Trees
Creating a Suffix Tree
In “Finding the Longest Multiple Repeat”, we introduced the suffix tree. This data
structure has a wide array of applications, one of which was to help us identify
long repeats in a genome. In that problem, we provided the tree as part of the
dataset, but a vital computational exercise is to create the suffix tree solely from a string.
Problem
Given a string having length , recall that its suffix tree

is defined by the following properties:
is a rooted tree having exactly leaves.

Every edge of is labeled with a substring of ,
where is the string formed by adding a placeholder
symbol $ to the end of . Figure 1. The suffix tree for s =
Every internal node of other than the root has at GTCCGAAGCTCCGG. Note that the
dollar sign has been appended to a
least two children;; i.e., it has degree at least 3. substring of the tree to mark the end
The substring labels for the edges leading down from a of s. Every path from the root to a leaf
corresponds to a unique suffix of
node to its children must begin with different symbols. GTCCGAAGCTCCGG, and each leaf
By concatenating the substrings along edges, each path is labeled with the location in s of
from the root to a leaf corresponds to a unique suffix of the suffix ending at that leaf.
.
Figure 1 contains an example of a suffix tree.
Given: A DNA string of length at most 1kbp.

Return: The substrings of encoding the edges of the suffix tree for . You may list these
substrings in any order.
Sample Dataset
ATAAATG$
Sample Output
AAATG$
G$
T
ATG$
TG$
A
A
AAATG$
G$
T
G$
$
Problem 80
Character-Based Phylogeny
Introduction to Character-Based Phylogeny
In “Creating a Character Table”, we discussed the construction of a character

table from a collection of characters represented by subsets of our taxa. However,
the ultimate goal is to be able to construct a phylogeny from this character table.
The issues at hand are that we want to ensure that we have enough characters to actually
construct a phylogeny, and that our characters do not conflict with each other.
Problem
Because a tree having nodes has edges (see “Completing a Tree”), removing a single edge
from a tree will produce two smaller, disjoint trees. Recall from “Creating a Character Table” that for
this reason, each edge of an unrooted binary tree corresponds to a split , where is a subset
of the taxa.
A consistent character table is one whose characters' splits do not conflict with the edge splits of
some unrooted binary tree on the taxa. More precisely, conflicts with if all
four intersections , , , and are nonempty. As a simple
example, consider the conflicting splits and .
More generally, given a consistent character table , an unrooted binary tree "models" if the
edge splits of agree with the splits induced from the characters of .
Given: A list of species ( ) and an -column character table in which the th column
denotes the th species.
Return: An unrooted binary tree in Newick format that models .
Sample Dataset
cat dog elephant mouse rabbit rat

011101
001101
001100
Sample Output
(dog,(cat,rabbit),(rat,(elephant,mouse)));
Problem 81
Counting Quartets
Introduction to Quartet-Based Phylogeny

In “Quartets”, we introduced partial splits modeling partial characters on a
collection of taxa. Our aim is to use the quartets inferred from partial splits to
construct a phylogeny on the taxa. This procedure is called quartet-based
phylogeny.
We could construct a phylogeny directly from a collection of partial splits, but it is
not immediately clear how many different splits we would need. Hence, our first
question is to ask how many quartets are required to be able to infer a tree;; in this
problem we will ask the reverse question of how many quartets can be inferred from a known tree.
Problem
A quartet is consistent with a binary tree if the quartet can be inferred from one of the
splits of (see “Quartets” for a description of inferring quartets from splits).
Let denote the total number of quartets that are consistent with .
Given: A positive integer ( ), followed by an unrooted binary tree in Newick
format on taxa.
Sample Dataset
6
(lobster,(cat,dog),(caterpillar,(elephant,mouse)));
Sample Output
15
Problem 82
Enumerating Unrooted Binary Trees
Seeing the Forest
In “Counting Unrooted Binary Trees”, we found a way to count the number of
unrooted binary trees representing phylogenies on taxa. Our observation was
that two such trees are considered distinct when they do not share the same
collection of splits.
Counting all these trees is one task, but actually understanding how to write them out in a list (i.e.,
enumerating them) is another, which will be the focus of this problem.
Problem
Recall the definition of Newick format from “Distances in
Trees” as a way of encoding trees. See Figure 1 for an
example of Newick format applied to an unrooted binary tree
whose five leaves are labeled (note that the same tree can
have multiple Newick representations).
Given: A collection of species names representing taxa.

Return: A list containing all unrooted binary trees whose Figure 1. This unrooted binary tree
may be represented in Newick
leaves are these taxa. Trees should be given in Newick format by (((a,b),c),(d,e));; another
format, with one tree on each line;; the order of the trees is way of encoding it is ((a,b),(c,(d,e))).
unimportant.
Sample Dataset
dog cat mouse elephant
Sample Output
(((mouse,cat),elephant))dog;
(((elephant,mouse),cat))dog;
(((elephant,cat),mouse))dog;
Problem 83
Genome Assembly Using Reads
Putting the Puzzle Together
In practical genome sequencing, even if we assume that reads have been
sequenced without errors, we have no idea of knowing immediately the particular
strand of DNA a read has come from.
Also, our reads may not have the same length. In 1995, Idury and Waterman proposed a way to
boost read coverage and achieve uniform read length by breaking long reads into overlapping -
mers for some fixed value of . For example, a 100 bp read could be split into 51 overlapping 50-
mers.
Problem
A directed cycle is simply a cycle in a directed graph in which the head of one edge is equal to the
tail of the next (so that every edge in the cycle is traversed in the same direction).
For a set of DNA strings and a positive integer , let denote the collection of all possible -mers
of the strings in .
Given: A collection of (error-free) reads of equal length (not exceeding 50 bp). In this dataset, for
some positive integer , the de Bruijn graph on consists of exactly two directed
cycles.
Return: A cyclic superstring of minimal length containing every read or its reverse complement.
Sample Dataset
AATCT
TGTAA
GATTA
ACAGA
Sample Output
GATTACA
Note
The reads "AATCT" and "TGTAA" are not present in the answer, but their reverse complements
"AGATT" and "TTACA" are present in the circular string (GATTACA).
Problem 84
Global Alignment with Constant Gap Penalty
Penalizing Large Insertions and Deletions
In dealing with global alignment in “Global Alignment with Scoring Matrix”, we
encountered a linear gap penalty, in which the insertion or deletion of a gap is
penalized by some constant times the length of the gap. However, this model is
not necessarily the most practical model, as one large rearrangement could have
inserted or deleted a long gap in a single step to transform one genetic string into another.
Problem
In a constant gap penalty, every gap receives some predetermined constant penalty, regardless of its
length. Thus, the insertion or deletion of 1000 contiguous symbols is penalized equally to that of a
single symbol.
Return: The maximum alignment score between and . Use:
Constant gap penalty equal to 5.
Sample Dataset
>Rosalind_79
PLEASANTLY
>Rosalind_41
MEANLY
Sample Output
13
Problem 85
Linguistic Complexity of a Genome
Getting Repetitive
We have seen that every genome contains a large number of repeats and noted
that the Alu repeat recurs around a million times on the human genome. Yet
exactly how repetitive is the human genome?
To frame such a vague question mathematically, we first need to make the observation that if the
genome were formed by adding nucleobases randomly, with each base having a 1/4 probability of
being added at each nucleotide position, then we should expect to see a huge number of different
substrings in the genome. Yet (to take a simple case) the genome containing only adenosine and
forming the DNA string "AAAAAA...AAA" has relatively very few distinct substrings.
Now, real genomes are formed by a process that chooses nucleotides somewhere in between
these two extreme cases, and so to quantify just how random this process is, we need to take the
percentage of distinct substrings appearing in a genome with respect to the maximum possible
number of distinct substrings that could appear in a genome of the same length.
Problem
Given a length string formed over an alphabet of size , let the "substring count"
denote the total number of distinct substrings of . Furthermore, let the "maximum substring count"
denote the maximum number of distinct substrings that could appear in a string of length
formed over .
The linguistic complexity of (written ) is equal to ;; in other words, represents
the percentage of observed substrings of to the total number that are theoretically possible. Note
that , with smaller values of indicating that is more repetitive.
As an example, consider the DNA string ( ) . In the following table, we
demonstrate that by considering the number of observed and possible length
substrings of , which are denoted by and , respectively. (Observe that
and .)
1 3 4
2 5 8
3 6 7
4 6 6
5 5 5
6 4 4
7 3 3
8 2 2
9 1 1
Total 35 40
Given: A DNA string of length at most 100 kbp.

Return: The linguistic complexity .
Sample Dataset
ATTTGGATT
Sample Output
0.875
Hint
Why does this problem follow “Encoding Suffix Trees”?
Problem 86
Local Alignment with Scoring Matrix
Aligning Similar Substrings
Whereas global alignment (see “Global Alignment with Scoring Matrix”) can be
helpful for comparing genetic strings of similar length that resemble each other,
often we will be presented with strings that are mostly dissimilar except for some
unknown region of the strings, which may represent a shared gene. To find such
genes, we need to modify global alignment to instead search for shared motifs in the form of locally
similar regions (recall “Finding a Shared Motif” and “Finding a Shared Spliced Motif”).
Using global alignment often fails to find shared motifs hidden in larger strings because (especially
if the similar region is found on different ends of the string) aligning the strings causes gap penalties
to rack up.
If we are only interested in comparing the regions of similarity, then we would like to have some
way of disregarding the parts of the strings that don't resemble each other. The way to do this is to
produce alignment scores for all possible pairs of substrings.
Problem
A local alignment of two strings and is an alignment of substrings and of and ,
respectively. Let denote the score of an optimal alignment of and with respect to some
predetermined alignment score.
Given: Two protein strings and in FASTA format (each having length at most 1000 aa).
Return: A maximum alignment score along with substrings and of and , respectively, which
produce this maximum alignment score (multiple solutions may exist, in which case you may output
any one). Use:
The PAM250 scoring matrix.

Linear gap penalty equal to 5.
Sample Dataset
>Rosalind_80
MEANLYPRTEINSTRING
>Rosalind_21
PLEASANTLYEINSTEIN
Sample Output
23
LYPRTEINSTRIN
LYEINSTEIN
Problem 87
Inferring Genotype from a Pedigree
Lying in Wait
Single gene disorders can be encoded by either dominant or recessive alleles. In
the latter case, the affected person usually has two healthy carrier parents, who
were usually unaware that their child could inherit a deadly or debilitating genetic
condition from them.
We know from Mendel's first law that any offspring of two heterozygous carriers has a 25% chance
of inheriting a recessive disorder. Knowing your own genotype is therefore important when deciding
to have children, and genetic screening will prove vital for preventive medicine in the coming years.
In this problem, we will consider an exercise in which we determine the probability of an organism
exhibiting each possible genotype for a factor knowing only the genotypes of the organism's
ancestors.
Problem
A rooted binary tree can be used to model the pedigree of an
individual. In this case, rather than time progressing from the
root to the leaves, the tree is viewed upside down with time
progressing from an individual's ancestors (at the leaves) to
the individual (at the root).
An example of a pedigree for a single factor in which only the
genotypes of ancestors are given is shown in Figure 1.
Given: A rooted binary tree in Newick format encoding

an individual's pedigree for a Mendelian factor whose alleles
are A (dominant) and a (recessive).
Return: Three numbers between 0 and 1, corresponding to Figure 1. The rooted binary tree
the respective probabilities that the individual at the root of whose Newick format is (aa,
will exhibit the "AA", "Aa" and "aa" genotypes. ((Aa,AA),AA)). Each leaf encodes the
genotype of an ancestor for the given
individual, which is represented by
Sample Dataset '?'.
((((Aa,aa),(Aa,Aa)),((aa,aa),(aa,AA))),Aa);
Sample Output
0.156 0.5 0.344
Problem 88
Maximizing the Gap Symbols of an Optimal Alignment
Adjusting Alignment Parameters
As we change the parameters contributing to alignment score, the nature of
alignments achieving the maximum score may change. One feature of maximum-
score alignments worthy of consideration is the number and size of their gaps. In
this problem, we would like to determine the maximum number of possible gaps
in any optimal alignment based solely on the parameter values chosen.
Problem
For the computation of an alignment score generalizing the edit alignment score, let denote the
score assigned to matched symbols, denote the score assigned to mismatched non-gap symbols,
and denote the score assigned a symbol matched to a gap symbol '-' (i.e., is a linear gap
penalty).
Given: Two DNA strings and in FASTA format (each of length at most 5000 bp).
Return: The maximum number of gap symbols that can appear in any maximum score alignment of
and with score parameters satisfying , , and .
Sample Dataset
>Rosalind_92
AACGTA
>Rosalind_47
ACACCTA
Sample Output
Problem 89
Identifying Maximal Repeats
Spies in the War Against Phages
In “Locating Restriction Sites”, we saw

how one weapon used by bacteria in their
age-old fight with phages is the use of
restriction enzymes. Another defense
Figure 1. A genomic region
mechanism found in the genomes of most bacteria and containing a CRISPR. Red
archaea centers on intervals of DNA called CRISPRs substrings correspond to CRISPR
repeats, and blue substrings
(Clustered Regularly Interspaced Short Palindromic correspond to unique spacers.
Repeats), which allow the cell to distinguish its own DNA Repeats are highly palindromic and
from that of phages or plasmids. fold into a hairpin loop when
transcribed.
Specifically, a CRISPR is an interval of DNA consisting of
identical repeats (approximately 23 to 47 bp long), alternating with unique intervals (approximately
21 to 72 bp long) called spacers;; see Figure 1. Spacers correspond to fragments of foreign DNA
that were integrated into the genome between repeats and serve as a memory bank for genetic
material captured from invading phages. As a result, spacers can be used to recognize and silence
invasive elements.
Specifically, CRISPRs are transcribed into RNA molecules, each consisting of a spacer flanked by
partial repeats. The small CRISPR RNAs, together with associated proteins translated from this
RNA, target foreign DNA that matches the CRISPR spacer. In eukaryotes, a similar process is
achieved by a process called RNA interference (RNAi).
To locate a CRISPR in a genome, we need to search for its repeats. We have already located long
repeats in “Finding the Longest Multiple Repeat”, but the case here is different because of the
repeats appearing in CRISPRS are relatively short. Instead, we are looking for repeated intervals
that cannot be lengthened in either direction (otherwise, we would intersect with a spacer).
Problem
A maximal repeat of a string is a repeated substring of having two occurrences and such
that and cannot be extended by one symbol in either direction in and still agree.
For example, "AG" is a maximal repeat in "TAGTTAGCGAGA" because even though the first two
occurrences of "AG" can be extended left into "TAG", the first and third occurrences differ on both
sides of the repeat;; thus, we conclude that "AG" is a maximal repeat. Note that "TAG" is also a
maximal repeat of "TAGTTAGCGAGA", since its only two occurrences do not still match if we extend
them in either direction.
Given: A DNA string of length at most 1 kbp.

Return: A list containing all maximal repeats of having length at least 20.
Sample Dataset
TAGAGATAGAATGGGTCCAGAGTTTTGTAATTTCCATGGGTCCAGAGTTTTGTAATTTATTATATAGAGAT
AGAATGGGTCCAGAGTTTTGTAATTTCCATGGGTCCAGAGTTTTGTAATTTAT
Sample Output
TAGAGATAGAATGGGTCCAGAGTTTTGTAATTTCCATGGGTCCAGAGTTTTGTAATTTAT
ATGGGTCCAGAGTTTTGTAATTT
Hint
How can we use the suffix tree of to find maximal repeats?
Problem 90
Multiple Alignment
Comparing Multiple Strings Simultaneously
In “Consensus and Profile”, we generalized the notion of Hamming distance to find an average case
for a collection of nucleic acids or peptides. However, this method only worked if
the polymers had the same length. As we have already noted in “Edit Distance”,
homologous strands of DNA have varying lengths because of the effect of
mutations inserting and deleting intervals of genetic material;; as a result, we need
to generalize the notion of alignment to cover multiple strings.
Problem
A multiple alignment of a collection of three or more strings is formed by adding gap symbols to the
strings to produce a collection of augmented strings all having the same length.
A multiple alignment score is obtained by taking the sum of an alignment score over all possible
pairs of augmented strings. The only difference in scoring the alignment of two strings is that two gap
symbols may be aligned for a given pair (requiring us to specify a score for matched gap symbols).
Given: A collection of four DNA strings of length at most 10 bp in FASTA format.
Return: A multiple alignment of the strings having maximum score, where we score matched
symbols 0 (including matched gap symbols) and all mismatched symbols -1 (thus incorporating a
linear gap penalty of 1).
Sample Dataset
>Rosalind_7
ATATCCG
>Rosalind_35
TCCG
>Rosalind_23
ATGTACTG
>Rosalind_44
ATGTCTG
Sample Output
-‐18
ATAT-‐CCG
-‐T-‐-‐-‐CCG
ATGTACTG
ATGT-‐CTG
Problem 91
Creating a Restriction Map
Genetic Fingerprinting
Recall that a restriction enzyme cuts the endpoints of a specific interval of DNA,
which must form a reverse palindrome that typically has length 4 or 6. The interval
of DNA cleaved by a given restriction enzyme is called its recognition sequence.
A single human chromosome is so long that a given recognition sequence will
occur frequently throughout the chromosome (recall from “Expected Number of
Restriction Sites” that a recognition sequence would be expected to occur several
times even in a short chromosome). Nevertheless, the small-scale mutations that
create diversity in the human genome (chiefly SNPs) will cause each human to have a different
collection of recognition sequences for a given restriction enzyme.
Genetic fingerprinting is the term applied to the general process of forming a limited picture of a
person's genetic makeup (which was traditionally cheaper than sequencing). The earliest
application of genetic fingerprinting inexpensive enough to be widely used in common applications,
like forensics and paternity tests, relied on a process called restriction digest. In this technique, a
sample of DNA is replicated artificially, then treated with a given restriction enzyme;; when the
enzyme cuts the DNA at restriction sites, it forms a number of fragments. A second process called
gel electrophoresis then separates these fragments along a membrane based on their size, with
larger pieces tending toward one end and smaller pieces tending toward the other. When the
membrane is stained or viewed with an X-ray machine, the fragments create a distinct banding
pattern, which typically differs for any two individuals.
These intervals can be thought of simply as the collection of distances between restriction sites in
the genome. Before the rapid advances of genome sequencing, biologists wanted to know if they
could use only these distances to reconstruct the actual locations of restriction sites in the
genome, forming a restriction map. Restriction maps were desired in the years before the advent
of sequencing, when any information at all about genomic makeup was highly coveted. The
application of forming a restriction map from cleaved restriction fragments motivates the following
problem.
Problem
For a set containing numbers, the difference multiset of

is the multiset defined as the collection of all positive
differences between elements of . As a quick example, if
, then we will have that .
If contains elements, then will contain one element

Figure 1. In the simplified figure
for each pair of elements from , so that contains above, we know that the dashed
elements (see combination statistic). You may note the segments came from a
chromosome;; we desire a collection
similarity between the difference multiset and the Minkowski of numbers whose differences
difference , which contains the elements of and match the lengths of the dotted
lines, which will correspond to the
their negatives. For the above set , is locations of restriction sites on the
. unknown chromosome. Taken from
Jones & Pevzner, An Introduction to
In practical terms, we can easily obtain a multiset Bioinformatics Algorithms.
corresponding to the distances between restriction sites on a
chromosome. If we can find a set whose difference multiset is equal to , then will
represent possible locations of these restriction sites. For an example, consult Figure 1.
Given: A multiset containing positive integers for some positive integer .
Return: A set containing nonnegative integers such that .
Sample Dataset
2 2 3 3 4 5 6 7 8 10
Sample Output
0 2 4 7 10
Problem 92
Counting Rooted Binary Trees
From Unrooted to Rooted Trees
Recall that a rooted binary tree is a binary tree for which the root is the only
node of degree 2. Such a tree differs from an unrooted binary tree only in the
existence of the root.
Different phylogenetic methods may be better suited to rooted or unrooted trees. If a method
produces an unrooted tree, then the root (i.e., the common ancestor of all taxa) could theoretically
be placed anywhere. Thus, there will be more rooted binary trees than unrooted binary trees on the
same number of taxa. The question is: how many more rooted trees are there?
Problem
As in the case of unrooted trees, say that we have a fixed collection of taxa labeling the leaves of a
rooted binary tree . You may like to verify that (by extension of “Counting Phylogenetic Ancestors”)
such a tree will contain internal nodes and total edges. Any edge will still encode a
split of taxa;; however, the two splits corresponding to the edges incident to the root of will be equal.
We still consider two trees to be equivalent if they have the same splits (which requires that they must
also share the same duplicated split to be equal).
Let represent the total number of distinct rooted binary trees on labeled taxa.
Sample Dataset
Sample Output
15
Problem 93
Sex-Linked Inheritance
Chromosomes Determine Sex
In “Independent Segregation of

Chromosomes”, we discussed how
chromosomes in diploid organisms form
pairs of homologs. It turns out that this is
not the case for one pair of chromosomes in animals. In
1905, Nettie Stevens and Edmund Wilson independently
discovered that male animals possess one chromosome
that is shorter than its partner, whereas female animals
instead have two long chromosomes. The shorter
chromosome earned the title of Y chromosome for its
stunted shape, whereas the longer chromosome became
known as the X chromosome. These two chromosomes
are aptly termed sex chromosomes, or allosomes, and Figure 1. Morgan's two experiments
on fruit fly eye color. In the first
we write the female sex chromosome genotype as experiment, a white-eyed male is
and the male genotype as . The remaining crossed with a purebred red-eyed
homologous chromosome pairs are called autosomes. female;; in the second experiment, a
red-eyed male is crossed with a
white-eyed female. The results of
Sex chromosomes are still passed on to gametes based
Morgan's expermients demonstrate
on the outcome of a coin flip, but egg cells (deriving from that eye color must be encoded by a
females) must always possess an X chromosome, so that recessive allele on the X
chromosome.
the sex of an individual is determined by whether it
receives an X or a Y chromosome from its father's sperm
cell.
Fast-forward five years to 1910 and the lab of Thomas Hunt Morgan, who is often considered the
first modern geneticist because of his tireless work to place Mendel's work on sound footing. One
of Morgan's many experiments with fruit flies (genus Drosophila) began as he noticed a number of
white-eyed males. When these white-eyed flies were crossed with purebred red-eyed females, their
progeny were all red-eyed, and yet crossing the second generation's red-eyed individuals with each
other produced some white-eyed males but exclusively red-eyed females. Strange results indeed.
Morgan's experiments are summarized in Figure 1, after which he concluded that the trait for eye
color in fruit flies must be sex linked, or encoded on a sex chromosome. More specifically, the
factor for white eye color is encoded by a recessive allele on the X chromosome. Because a male
only has one copy of the X chromosome, having only one recessive allele will cause the individual
to exhibit white eyes, whereas a female fly requires both copies of the recessive allele to possess
white eyes.
X-linked recessive traits are manifested in males much more often than in females, because a male
only needs to receive a recessive allele from his mother to exhibit the trait: in the case of genetic
conditions, half of all male children born to carrier mothers will inherit the condition.
Problem
The conditional probability of an event given another event , written , is equal to
divided by .
Note that if and are independent, then must be equal to , which
results in . This equation offers an intuitive view of independence: the probability
of , given the occurrence of event , is simply the probability of (which does not depend on ).
In the context of sex-linked traits, genetic equilibrium requires that the alleles for a gene are
uniformly distributed over the males and females of a population. In other words, the distribution of
alleles is independent of sex.
Given: An array of length for which represents the proportion of males in a population
exhibiting the -th of total recessive X-linked genes. Assume that the population is in genetic
equilibrium for all genes.
Return: An array of length in which equals the probability that a randomly selected
female will be a carrier for the -th gene.
Sample Dataset
0.1 0.5 0.8
Sample Output
0.18 0.5 0.32
Problem 94
Phylogeny Comparison with Split Distance
Quantifying Binary Tree Comparison
We may often obtain two different phylogenies on the same collection of taxa from
different sets of data. As a result, we would like to have a way of quantifying how
much the two phylogenies differ. In the simplest case, we would like to compare
the characters of two phylogenies.
Recall from “Counting Unrooted Binary Trees” that two unrooted binary trees are equivalent when
they have the same set of splits;; recall also (by extension of “Counting Phylogenetic Ancestors”)
that any unrooted binary tree on taxa must have nontrivial splits.
Problem
Define the split distance between two unrooted binary trees as the number of nontrivial splits
contained in one tree but not the other.
Formally, if denotes the number of nontrivial splits shared by unrooted binary trees and
, Then their split distance is .
Given: A collection of at most 3,000 species taxa and two unrooted binary trees and on
these taxa in Newick format.
Return: The split distance .
Sample Dataset
dog rat elephant mouse cat rabbit

(rat,(dog,cat),(rabbit,(elephant,mouse)));
(rat,(cat,dog),(elephant,(mouse,rabbit)));
Sample Output
Problem 95
The Wright-Fisher Model of Genetic Drift
Hardy-Weinberg Revisited
The principle of genetic equilibrium is an idealistic model for population genetics
that simply cannot hold for all genes in practice. For one, evolution has proven too
powerful for equilibrium to possibly hold. At the same time, evolution works on the
scale of eons, and at any given moment in time, most populations are essentially
stable.
Yet we could overlook the inevitable effects of simple random chance in disrupting the allelic
frequency for a given gene, a phenomenon called genetic drift.
In this problem, we would like to obtain a simple mathematical model of genetic drift, and so we will
need to make a number of simplifying assumptions. First, assume that individuals from different
generations do not mate with each other, so that generations exist as discrete, non-overlapping
quantities. Second, rather than selecting pairs of mating organisms, we simply randomly select the
alleles for the individuals of the next generation based on the allelic frequency in the present
generation. Third, the population size is stable, so that we do not need to take into account the
population growing or shrinking between generations. Taken together, these three assumptions
make up the Wright-Fisher model of genetic drift.
Problem
Consider flipping a weighted coin that gives "heads" with some fixed probability (i.e., is not
necessarily equal to 1/2).
We generalize the notion of binomial random variable from “Independent Segregation of Chromosomes”
to quantify the sum of the weighted coin flips. Such a random variable takes a value of if a
sequence of independent "weighted coin flips" yields "heads" and "tails." We write that
.
To quantify the Wright-Fisher Model of genetic drift, consider a population of diploid individuals,
whose chromosomes possess copies of the dominant allele. As in “Counting Disease
Carriers”, set . Next, recall that the next generation must contain exactly individuals.
These individuals' alleles are selected independently: a dominant allele is chosen with probability
, and a recessive allele is chosen with probability .
Given: Positive integers ( ), ( ), ( ) and ( ).
Return: The probability that in a population of diploid individuals initially possessing copies of
a dominant allele, we will observe after generations at least copies of a recessive allele. Assume
the Wright-Fisher model.
Sample Dataset
4 6 2 1
Sample Output
0.772
Problem 96
Alignment-Based Phylogeny
From Characters Toward Alignments
In “Creating a Character Table from Genetic Strings”, we used strings to create a
collection of characters from which we could create a phylogeny. However, the
strings all had to share the same length, which was a problem. In practice, we
would like to create a phylogeny from genetic strings having differing lengths;;
specifically, our aim is to construct a phylogeny from a multiple alignment.
Unfortunately, constructing a phylogeny from the ground up based only on an alignment can be
difficult. In order to produce an efficient solution, we will need to assume that the structure of the
phylogeny has already been provided (perhaps from character-based methods), and our aim instead
is to reconstruct the genetic strings corresponding to the internal nodes (i.e., ancestors) in the tree.
The ancestor strings should have the property that the total number of point mutations separating
adjacent nodes in the tree is minimized (in keeping with parsimony).
Problem
Say that we have taxa represented by strings with a multiple alignment inducing
corresponding augmented strings .
Recall that the number of single-symbol substitutions required to transform one string into another is
the Hamming distance between the strings (see “Counting Point Mutations”). Say that we have a
rooted binary tree containing at its leaves and additional strings
at its internal nodes, including the root (the number of internal nodes is
by extension of “Counting Phylogenetic Ancestors”). Define as the sum of
over all edges in :
Thus, our aim is to minimize .
Given: A rooted binary tree on ( ) species, given in Newick format, followed by a
multiple alignment of ( ) augmented DNA strings having the same length (at most 300 bp)
corresponding to the species and given in FASTA format.
Return: The minimum possible value of , followed by a collection of DNA strings to be
assigned to the internal nodes of that will minimize (multiple solutions will exist, but you
need only output one).
Sample Dataset
(((ostrich,cat)rat,(duck,fly)mouse)dog,(elephant,pikachu)hamster)robot;
>ostrich
AC
>cat
CA
>duck
T-‐
>fly
GC
>elephant
-‐T
>pikachu
AA
Sample Output
8
>rat
AC
>mouse
TC
>dog
AC
>hamster
AT
>robot
AC
Note
Given internal strings minimizing , the alignment between any two adjacent strings is not
necessarily an optimal global paired alignment. In other words, it may not be the case that
is equal to the edit distance .
Problem 97
Assessing Assembly Quality with N50 and N75
How Well Assembled Are Our Contigs?
As we have stated, the goal of genome sequencing is to create contigs that are
as long as possible. Thus, after fragment assembly, it is important to possess
statistics quantifying how well-assembled our contigs are.
First and foremost, we demand a measure of what percentage of the assembled genome is made
up of long contigs. Our first question is then: if we select contigs from our collection, how long do
the contigs need to be to cover 50% of the genome?
Problem
Given a collection of DNA strings representing contigs, we use the N statistic NXX (where XX ranges
from 01 to 99) to represent the maximum positive integer such that the total number of nucleotides
of all contigs having length is at least XX% of the sum of contig lengths. The most commonly
used such statistic is N50, although N75 is also worth mentioning.
Given: A collection of at most 1000 DNA strings (whose combined length does not exceed 50 kbp).
Return: N50 and N75 for this collection of strings.
Sample Dataset
GATTACA
TACTACTAC
ATTGAT
GAAGA
Sample Output
7 6
Extra Information
For an explanation of the results obtained in the sample above, contigs of length at least 7 total 7 +
9 = 16 bp, which is more than 50% of the total 27). Contigs of length at least 8 total only 9 bp (less
than 50%).
Contigs of length at least 6 total 6 + 7 + 9 = 22 bp, which is more than 75% of all base pairs.
Contigs of length at least 7 total only 16 bp (less than 75%).
Problem 98
Fixing an Inconsistent Character Set
Pitfalls of Character-Based Phylogeny
In “Character-Based Phylogeny”, we asked for the construction of an unrooted
binary tree from a consistent character table. However, the assumption of
consistency is often inaccurate, as many character collections derived from real
data are inconsistent, owing to the fact that the reinforcement of mutations by
evolution can cause species to lose features over time, evolve to produce the same character on
different evolutionary paths, or revert to a past character. This issue arises even when using
genetic characters taken from SNPs, as point mutations can be undone.
As an example of why using characters can lead us astray, let's return to our first example of a
character introduced in “Character-Based Phylogeny”. There, we learned that dinosaurs may be
divided into the two Orders Saurischia and Ornithischia depending on hip-bone shape: the former
have "lizard hips," whereas the latter have "bird hips." Adding to this information the fact that birds
are widely believed to descend from dinosaurs, we would guess that birds derive from
ornithischians. Yet this is not the case: birds derive from theropods, a suborder of the saurischians!
The shared hip bone shape with ornithischians is either simply coincidence or caused by the
"convergence" of bird hip shape with that of ornithischians along their different evolutionary paths.
Another example of a character that would be ill-suited for phylogenetic analysis is the presence or
absence of wings in insects. Many wingless modern species wingless modern species have
evolved from wildly differing ancestors that lost their wings independently of each other.
If we divided a collection of taxa based on either of these characters, many different taxa would be
lumped together when they do not in fact share a recent common ancestor, which could have
disastrous consequences when trying to assign characters to the splits of a phylogeny.
The moral is that we must select our characters carefully, although the Catch-22 is that we don't
know in advance which characters are the most appropriate to use until we actually start
constructing phylogenies. At the same time, if we err on the side of caution, then using too few
characters might not provide us with enough splits to generate an unrooted binary tree, thus
inducing an enormous number of possible phylogenies (recall “Counting Unrooted Binary Trees” and
how quickly the total number of trees grows with the number of taxa).
Problem
A submatrix of a matrix is a matrix formed by selecting rows and columns from and taking
only those entries found at the intersections of the selected rows and columns. We may also think of a
submatrix as formed by deleting the remaining rows and columns from .
Given: An inconsistent character table on at most 100 taxa.
Return: A submatrix of representing a consistent character table on the same taxa and formed
by deleting a single row of . (If multiple solutions exist, you may return any one.)
Sample Dataset
100001
000110
111000
100111
Sample Output
000110
100001
100111
Problem 99
Wright-Fisher's Expected Behavior
Reaching Population Equilibrium
In “The Wright-Fisher Model of Genetic Drift”, we introduced the Wright-Fisher
model of genetic drift. Although the effects of genetic drift are inevitable, we should
be able to quantify how many alleles for a given trait will remain in the next
generation.
Intuitively, because Wright-Fisher demands that we randomly and independently select alleles for
the next generation based off the allele frequency of the present generation, we would hope that on
average this frequency would illustrate a stabilizing effect: that is, the expected frequency in the
next generation should equal the allele frequency in the current generation. In this problem, we will
see if the mathematics matches our intuition.
Problem
In “The Wright-Fisher Model of Genetic Drift”, we generalized the concept of a binomial random variable
as a "weighted coin flip." It is only natural to calculate the expected value of such a random
variable.
For example, in the case of unweighted coin flips (i.e., ), our intuition would indicate that
is ;; what should be the expected value of a binomial random variable?
Given: A positive integer ( ) followed by an array of length ( )

containing numbers between and . Each element of can be seen as representing a probability
corresponding to an allele frequency.
Return: An array of length for which is the expected value of ;; in terms of
Wright-Fisher, it represents the expected allele frequency of the next generation.
Sample Dataset
17
0.1 0.2 0.3
Sample Output
1.7 3.4 5.1
Problem 100
The Founder Effect and Genetic Drift
Strength in Numbers
Charles Darwin is known first and foremost for his notion of natural selection,
the elegant statistical fact that changes in populations are attributable to the
observation that organisms better equipped to handle their environment are more
likely to survive and reproduce, thus passing on their beneficial traits to the next
generation. As a result of natural selection, populations can change greatly over a long time.
A lesser known aspect of Darwin's evolutionary theory dictates how new species are actually
created. Darwin noted that the only way for a population to grow so distinct that it would actually
split off and form a new species would be if the population were isolated for a very long period. This
notion that isolation forms new species was validated by Darwin's observation that the tiny
Galapagos islands in the South Pacific enjoy a diversity of species rivaling that of a much larger
ecosystem.
Isolated populations also tend to be small, strengthening the effects of genetic drift. To take an
extreme example, consider a population of only 2 organisms that are both heterozygous for a given
factor. Note that there is a 1/8 chance that 2 offspring of these organisms will possess only
recessive alleles or only dominant alleles for the factor, thus wiping out the other allele completely.
In general, the principle stating that mutations (both positive and negative) can randomly attain
higher proportions in small, isolated communities than they would in large populations, is known as
the founder effect. An infamous example of the founder effect on human populations occurs in
Pennsylvania, where the Amish community is at risk for a much greater incidence of Ellis-van
Creveld syndrome, a single gene disorder causing a slew of defects, including additional fingers
and toes (polydactyly). The condition has been traced to a single couple in the original Amish
settlers, and it is still preserved in elevated percentages because of the community's isolationism.
In this problem, we would like to apply the Wright-Fisher model of genetic drift to understand the
power of the founder effect. Specifically, we will quantify the likelihood that an allele will be
completely annihilated in a small population after a number of generations.
Problem
Given: Two positive integers and , followed by an array containing integers between 0
and . represents the number of recessive alleles for the -th factor in a population of
diploid individuals.
Return: An matrix for which represents the common logarithm of the probability
that after generations, no copies of the recessive allele for the -th factor will remain in the
population. Apply the Wright-Fisher model.
Sample Dataset
4 3
0 1 2
Sample Output
0.0 -‐0.463935575821 -‐0.999509892866

0.0 -‐0.301424998891 -‐0.641668367342
0.0 -‐0.229066698008 -‐0.485798552456
Problem 101
Global Alignment with Scoring Matrix and Affine Gap
Penalty
Mind the Gap
In “Global Alignment with Scoring Matrix”, we considered a linear gap penalty, in
which each inserted/deleted symbol contributes the exact same amount to the
calculation of alignment score. However, as we mentioned in “Global Alignment
with Constant Gap Penalty”, a single large insertion/deletion (due to a
rearrangement is then punished very strictly, and so we proposed a constant gap penalty.
Yet large insertions occur far more rarely than small insertions and deletions. As a result, a more
practical method of penalizing gaps is to use a hybrid of these two types of penalties in which we
charge one constant penalty for beginning a gap and another constant penalty for every additional
symbol added or deleted.
Problem
An affine gap penalty is written as , where is the length of the gap, is a positive
constant called the gap opening penalty, and is a positive constant called the gap extension
penalty.
We can view the gap opening penalty as charging for the first gap symbol, and the gap extension
penalty as charging for each subsequent symbol added to the gap.
For example, if and , then a gap of length 1 would be penalized by 11 (for an average
cost of 11 per gap symbol), whereas a gap of length 100 would have a score of 110 (for an average
cost of 1.10 per gap symbol).
Consider the strings "PRTEINS" and "PRTWPSEIN". If we use the BLOSUM62 scoring matrix and an
affine gap penalty with and , then we obtain the following optimal alignment.
PRT-‐-‐-‐EINS
||| |||
PRTWPSEIN-‐
Matched symbols contribute a total of 32 to the calculation of the alignment's score, and the gaps cost
13 and 11 respectively, yielding a total score of 8.
Return: The maximum alignment score between and , followed by two augmented strings
and representing an optimal alignment of and . Use:

Gap opening penalty equal to 11.
Gap extension penalty equal to 1.
Sample Dataset
>Rosalind_49
PRTEINS
>Rosalind_47
PRTWPSEIN
Sample Output
8
PRT-‐-‐-‐EINS
PRTWPSEIN-‐
Problem 102
Genome Assembly with Perfect Coverage and Repeats
Repeats: A Practical Assembly Difficulty
Genome assembly is straightforward if we know in advance that the de Bruijn
graph has exactly one directed cycle (see “Genome Assembly with Perfect
Coverage”).
In practice, a genome contains repeats longer than the length of the k-mers that we wish to use to
assemble the genome. Such repeats increase the number of cycles present in the de Bruijn graph
for these -mers, thus preventing us from assembling the genome uniquely.
For example, consider the circular string (ACCTCCGCC), along with a collection of error-free
reads of length 3, exhibiting perfect coverage and taken from the same strand of an interval of DNA.
The corresponding de Bruijn graph (where edges correspond to 3-mers and nodes correspond
to 2-mers) has at least two directed cycles: one giving the original circular string (ACCTCCGCC),
and another corresponding to the misfit (ACCGCCTCC).
Also, note that these cycles are not simple cycles, as the node corresponding to "CC" is visited
three times in each cycle.
To generalize the problem of genome assembly from a de Bruijn graph to the case of genomes
containing repeats, we therefore must add a constraint: in a cycle corresponding to a valid
assembly, every 3-mer must appear as many times in the cycle as it does in our collection of
reads (which correspond to all 3-mers in the original string).
Problem
Recall that a directed cycle is a cycle in a directed graph in which the head of one edge is equal to the
tail of the following edge.
In a de Bruijn graph of -mers, a circular string is constructed from a directed cycle
is given by . That is, because
the final symbols of overlap with the first symbols of , we simply tack on the -th
symbol of to , then iterate the process.
For example, the circular string assembled from the cycle "AC" "CT" "TA" "AC" is simply
(ACT). Note that this string only has length three because the 2-mers "wrap around" in the string.
If every -mer in a collection of reads occurs as an edge in a de Bruijn graph cycle the same number
of times as it appears in the reads, then we say that the cycle is "complete."
Given: A list of error-free DNA -mers ( ) taken from the same strand of a
circular chromosome (of length ).
Return: All circular strings assembled by complete cycles in the de Bruijn graph of . The
strings may be given in any order, but each one should begin with the first -mer provided in the
input.
Sample Dataset
CAG
AGT
GTT
TTT
TTG
TGG
GGC
GCG
CGT
GTT
TTC
TCA
CAA
AAT
ATT
TTC
TCA
Sample Output
CAGTTCAATTTGGCGTT
CAGTTCAATTGGCGTTT
CAGTTTCAATTGGCGTT
CAGTTTGGCGTTCAATT
CAGTTGGCGTTCAATTT
CAGTTGGCGTTTCAATT
Problem 103
Overlap Alignment
Overlapping Reads with Errors
As also mentioned in “Error Correction in Reads”, the sequencing machines that
identify reads can make errors. However, the problem that we considered in
“Genome Assembly as Shortest Superstring” assumed that all reads are error-
free.
Thus, rather than trying to overlap reads exactly, we will instead do so approximately. The key to
do this is to move toward methods that incorporate alignments. Yet neither global nor local
alignment is appropriate for this task. Global alignment will attempt to align the entire reads, when
we know that only the overlapping parts of the reads are relevant. For that matter, we may identify
an optimal local alignment that does not correspond to an overlap.
As a result, we need a specific type of local alignment that aligns only the overlapping parts of two
strings.
Problem
An overlap alignment between two strings and is a local alignment of a suffix of with a prefix of
. An optimal overlap alignment will therefore maximize an alignment score over all such substrings of
and .
The term "overlap alignment" has also been used to describe what Rosalind defines as a semiglobal
alignment. See “Semiglobal Alignment” for details.
Given: Two DNA strings and in FASTA format, each having length at most 10 kbp.
Return: The score of an optimal overlap alignment of and , followed by an alignment of a suffix
of and a prefix of achieving this optimal score. Use an alignment score in which matching
symbols count +1, substitutions count -2, and there is a linear gap penalty of 2. If multiple optimal
alignments exist, then you may return any one.
Sample Dataset
>Rosalind_54
CTAAGGGATTCCGGTAATTAGACAG
>Rosalind_45
ATAGACCATATGTCAGTGACTGTGTAA
Sample Output
1
ATTAGAC-‐AG
AT-‐AGACCAT
Citation
This problem follows Jones & Pevzner, An Introduction to Bioinformatics Algorithms, problem 6.22.
Problem 104
Quartet Distance
Another Tree Distance
In “Phylogeny Comparison with Split Distance”, we examined the split distance for
comparison of different phylogenies on the same collection of taxa.
Yet quartet-based phylogeny offers another way in which two phylogenies can be
compared (see “Quartets” and “Counting Quartets”). Specifically, we wonder how many quartets
can be inferred from one tree but not inferred from the other.
Problem
In “Counting Quartets”, we found an expression for , the number of quartets that can be inferred
from an unrooted binary tree containing taxa.
If and are both unrooted binary trees on the same taxa, then we now let denote
the number of inferred quartets that are common to both trees. The quartet distance between and
, is the number of quartets that are only inferred from one of the trees. More precisely,
.
Given: A list containing taxa ( ) and two unrooted binary trees and on the given
taxa. Both and are given in Newick format.
Return: The quartet distance .

Sample Dataset
A B C D E
(A,C,((B,D),E));
(C,(B,D),(A,E));
Sample Output
Problem 105
Finding a Motif with Modifications
Finding Mutated Motifs
We have discussed at length the importance of motif finding in biology for genetic
strings. However, searching for exact substring matches is of little use in
applications because a motif can vary under the effect of mutation. Fortunately,
we already possess functions like edit distance for quantifying the similarity of two
strings.
Furthermore, recall that each chromosome is made up of a large number of genes (on average,
each human chromosome contains over 1,000 genes). Therefore, to determine whether a newly
sequenced chromosome contains a given gene, neither local nor global alignment applies.
One possible alignment variant for finding genes is semiglobal alignment, which we discuss in
“Semiglobal Alignment”;; yet semiglobal alignment only allows us to disregard gaps at the end of
the alignment. To find a known gene in a new chromosome, we need to instead align the gene
against intervals of the chromosome, a problem that calls for an entirely new algorithmic variation of
alignment.
Problem
Given a string and a motif , an alignment of a substring of

against all of is called a fitting alignment. Our aim is to
find a substring of that maximizes an alignment score
with respect to . Figure 1. Global, local, and fitting
alignments of strings v =
Note that more than one such substring of may exist, GTAGGCTTAAGGTTA and w =
depending on the particular strings and alignment score used. TAGATA with respect to mismatch
One candidate for scoring function is the one derived from edit score. Note that in the fitting
alignment, a substring of v must be
distance;; In this problem, we will consider a slightly different aligned against all of w. Taken from
alignment score, in which all matched symbols count as +1 Jones & Pevzner, An Introduction to
Bioinformatics Algorithms
and all mismatched symbols (including insertions and
deletions) receive a cost of -1. Let's call this scoring function
the mismatch score. See Figure 1 for a comparison of global, local, and fitting alignments with
respect to mismatch score.
Given: Two DNA strings and , where has length at most 10 kbp and represents a motif of
length at most 1 kbp.
Return: An optimal fitting alignment score with respect to the mismatch score defined above,
followed by an optimal fitting alignment of a substring of against . If multiple such alignments exist,
then you may output any one.
Sample Dataset
>Rosalind_54
GCAAACCATAAGCCCTACGTGCCGCCTGTTTAAACTCGCGAACTGAATCTTCTGCTTCACGGTGAAAGTAC
CACAATGGTATCACACCCCAAGGAAAC
>Rosalind_46
GCCGTCAGGCTGGTGTCCG
Sample Output
5
ACCATAAGCCCTACGTG-‐CCG
GCCGTCAGGC-‐TG-‐GTGTCCG
Citation
This problem follows Jones & Pevzner, An Introduction to Bioinformatics Algorithms, Problem 6.23.
Problem 106
Semiglobal Alignment
Gaps on the Ends are Free
We have covered both global and local alignments. However, sometimes we need
a hybrid approach that avoids the weaknesses of these two methods. One such
alternate approach is that of fitting alignments outlined in “Finding a Motif with
Modifications”.
Another tactic is to allow ourselves to trim off gaps appearing on the ends of a global alignment for
free;; this is relevant if one of our strings to be aligned happens to contain additional symbols on the
ends that are not relevant for the particular alignment at hand.
Problem
A semiglobal alignment of strings and is an alignment in which any gaps appearing as prefixes
or suffixes of and do not contribute to the alignment score.
Semiglobal alignment has sometimes also been called "overlap alignment". Rosalind defines overlap
alignment differently (see “Overlap Alignment”).
Given: Two DNA strings and in FASTA format, each having length at most 10 kbp.
Return: The maximum semiglobal alignment score of and , followed by an alignment of and
achieving this maximum score. Use an alignment score in which matching symbols count +1,
substitutions count -1, and there is a linear gap penalty of 1. If multiple optimal alignments exist, then
you may return any one.
Sample Dataset
>Rosalind_79
CAGCACTTGGATTCTCGG
>Rosalind_98
CAGCGTGG
Sample Output
4
CAGCA-‐CTTGGATTCTCGG
-‐-‐-‐CAGCGTGG-‐-‐-‐-‐-‐-‐-‐-‐
Citation
This problem follows Jones & Pevzner, An Introduction to Bioinformatics Algorithms, Problem 6.24.
Problem 107
Finding All Similar Motifs
The Case of Mutated Repeats
In “Finding a Motif with Modifications”, we considered a problem in which we were
given a motif and a long string (perhaps representing a genome), and we aimed to
find the "closest" substring of the long string to the motif. In that problem,
"closest" was defined as a minimum with respect to edit distance.
Yet there may be multiple substring candidates from the genome that achieve the minimum
distance to the motif;; this situation might occur in practice when the motif forms a repeat that
occurs multiple times with variations deriving from mutations.
In this problem, we would like to find all substrings of a genome that are within a certain fixed
distance of the desired motif.
Problem
Given: A positive integer ( ), a DNA string of length at most 5 kbp representing a motif,
and a DNA string of length at most 50 kbp representing a genome.
Return: All substrings of such that the edit distance is less than or equal to . Each
substring should be encoded by a pair containing its location in followed by its length.
Sample Dataset
2
ACGTAG
ACGGATCGGCATCGT
Sample Output
1 4
1 5
1 6
Problem 108
Local Alignment with Affine Gap Penalty
Building Upon Local Alignments
We have thus far worked with local alignments with a linear gap penalty and
global alignments with affine gap penalties (see “Local Alignment with Scoring
Matrix” and “Global Alignment with Scoring Matrix and Affine Gap Penalty”).
It is only natural to take the intersection of these two problems and find an optimal local alignment
given an affine gap penalty.
Problem
Given: Two protein strings and in FASTA format (each having length at most 10,000 aa).
Return: The maximum local alignment score of and , followed by substrings and of and ,
respectively, that correspond to the optimal local alignment of and . Use:

Gap opening penalty equal to 11.
Gap extension penalty equal to 1.
If multiple solutions exist, then you may output any one.

Sample Dataset
>Rosalind_8
PLEASANTLY
>Rosalind_18
MEANLY
Sample Output
12
LEAS
MEAN
Problem 109
Isolating Symbols in Alignments
How Much Does it Cost to Align Two Symbols?
As we saw in “Counting Optimal Alignments”, there will usually be a huge number
of different optimal alignments of two given strings. In this problem, which
represents a first attempt to understand how much optimal alignments can differ,
we will select two symbols at a time from the two strings and ask how much the
maximum alignment score can differ from the optimal score if we demand that these two symbols
must be aligned (i.e., implying that one symbol must be substituted for the other).
Problem
Say that we have two strings and of respective lengths and and an alignment score. Let's
define a matrix corresponding to and by setting equal to the maximum score of any
alignment that aligns with . So each entry in can be equal to at most the maximum score
of any alignment of and .
Given: Two DNA strings and in FASTA format, each having length at most 1000 bp.
Return: The maximum alignment score of a global alignment of and , followed by the sum of all
elements of the matrix corresponding to and that was defined above. Apply the mismatch score
introduced in “Finding a Motif with Modifications”.
Sample Dataset
>Rosalind_35
ATAGATA
>Rosalind_5
ACAGGTA
Sample Output
3
-‐139
Citation
This problem follows Jones & Pevzner, An Introduction to Bioinformatics Algorithms, Problem 6.21
Hint
For the sample dataset
Problem 110
Identifying Reversing Substitutions
Reversions Complicate Phylogenies
In “Fixing an Inconsistent Character Set”,

we mentioned how the construction of a
phylogeny can be complicated by a the
reversion of a character to a past state.
For that matter, in calculating Hamming distance and edit
distance, the assumption of parsimony required us to
assume that if some nucleotide base or amino acid is
aligned with an identical symbol in two genetic strings,
then it has not changed on the evolutionary path between
the two taxa.
However, this model is too strict in practice, where a base Figure 1. Illustration of an amino
or amino acid can change to another state and then acid's reversing substitution after
two point mutations.
change back as the result of two point mutations, which is
called a reversing substitution;; see Figure 1. In the case
of DNA, the presence of only four bases makes randomly occurring reversing substitutions
common;; these substitutions will carry over into amino acid language via transcription and
translation.
Unfortunately, with the possible exception of experimental evolution in bacteria, we lack the luxury
of knowing the ancestral state of a nucleic acid strand. Instead, we must infer its most probable
ancestor from homologous strands. To do so, we may use characters to construct a phylogeny
(see “Character-Based Phylogeny”), then apply alignment-based phylogeny to infer strings for the
tree's internal nodes (see “Alignment-Based Phylogeny”). Only once we have an adequate picture
of the entire phylogeny, including its internal nodes, can we hope to identify reversing substitutions.
Problem
For a rooted tree whose internal nodes are labeled with genetic strings, our goal is to identify
reversing substitutions in . Assuming that all the strings of have the same length, a reversing
substitution is defined formally as two parent-child string pairs and along with a position
index , where:
there is a path in from down to ;;

;; and
if is on the path connecting to , then .
In other words, the third condition demands that a reversing substitution must be contiguous: no other
substitutions can appear between the initial and reversing substitution.
Given: A rooted binary tree with labeled nodes in Newick format, followed by a collection of at
most 100 DNA strings in FASTA format whose labels correspond to the labels of . We will assume
that the DNA strings have the same length, which does not exceed 400 bp).
Return: A list of all reversing substitutions in (in any order), with each substitution encoded by
the following three items:
the name of the species in which the symbol is first changed, followed by the name of the species
in which it changes back to its original state
the position in the string at which the reversing substitution occurs;; and
the reversing substitution in the form original_symbol->substituted_symbol->reverted_symbol.
Sample Dataset
(((ostrich,cat)rat,mouse)dog,elephant)robot;
>robot
AATTG
>dog
GGGCA
>mouse
AAGAC
>rat
GTTGT
>cat
GAGGC
>ostrich
GTGTC
>elephant
AATTC
Sample Output
dog mouse 1 A-‐>G-‐>A
dog mouse 2 A-‐>G-‐>A
rat ostrich 3 G-‐>T-‐>G
rat cat 3 G-‐>T-‐>G
dog rat 3 T-‐>G-‐>T

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What is the purpose of installing Python?

What is the purpose of installing Python?

What are some basic data types in Python?

What are some basic data types in Python?

Bioinformatics Programming 2013

You'll see a window containing three arrows, like so:

print "Hello, World!"

Congratulations! You just ran your first program in Python!

Variables and Some Arithmetic

a -­‐ b is 300

String operations differ slightly from operations on numbers:

Given: Two positive integers and , each less than 1000.

1. The dataset changes every time you click "Download dataset".

Strings and lists

Your output should be:

tea_party[1] = 'Cheshire Cat'

March Hare, Cheshire Cat, Dormouse, Alice

This code outputs the following:

March Hare, Cheshire Cat, Dormouse, Alice, Jabberwocky

Conditions and Loops

names = ['Alice', 'Bob', 'Charley']

print range(5, 12)

Given: Two positive integers and ( ).

You can use a % 2 == 1 to test if a is odd.

Reading and Writing

r -­ read mode (the file is opened for reading)

for line in f:

'Beautiful is better than ugly.\n'.split() returns ['Beautiful', 'is', 'better',

'Explicit, is better, than implicit.'.split(",") returns ['Explicit', ' is

'Simple is\nbetter than\ncomplex.\n'.splitlines() returns ['Simple is', 'better

You can then write your data using .write() method.

f.write('Any data you want to write into file')

inscription = ['Rosalind Elsie Franklin ', 1920, 1958]

for i in inscription:

Given: A file containing at most 1000 lines.

`Bravely bold Sir Robin rode forth from Camelot

Yes, brave Sir Robin turned about

Intro to Python dictionary

phones = {'Zoe':'232-­‐43-­‐58', 'Alice':'165-­‐88-­‐56'}

Output should be:

{'Bill': '342-­‐18-­‐25', 'Zoe': '658-­‐99-­‐55', 'Alice': '165-­‐88-­‐56'}

{'KEY': 3, 'Key': 2, 'key': 1}

if 'Peter' in phones:

We don't know Peter's phone

phones = {'Zoe':'232-­‐43-­‐58', 'Alice':'165-­‐88-­‐56'}

Given: A string of length at most 10000 letters.

for word in str.split(' '):

for key, value in dict.items():

A Rapid Introduction to Molecular Biology

Making up all living material, the cell is

The nucleic acid monomer is called a nucleotide and is

Given: A DNA string of length at most 1000 nt.

20 12 17 21

The Second Nucleic Acid

In “Counting DNA Nucleotides”, we

Yet a second nucleic acid exists alongside DNA in the

Given: A DNA string having length at most 1000 nt.

The Secondary and Tertiary Structures of DNA

a -‐ b is 300

r - read mode (the file is opened for reading)

phones = {'Zoe':'232-‐43-‐58', 'Alice':'165-‐88-‐56'}

{'Bill': '342-‐18-‐25', 'Zoe': '658-‐99-‐55', 'Alice': '165-‐88-‐56'}

phones = {'Zoe':'232-‐43-‐58', 'Alice':'165-‐88-‐56'}

Rearrangements Power Large-Scale Genomic Changes

The Billion-Year War

Because RNA is single-stranded, you

In the greater three-dimensional world, the base pairing

-‐5.737 -‐5.217 -‐5.263 -‐5.360 -‐5.958 -‐6.628 -‐7.009