Abstract
In this work we integrate conventional mRNA expression profiles with miRNA expressions using the knowledge of their validated or predicted interactions in order to improve class prediction in genetically determined diseases. The raw mRNA and miRNA expression features become enriched or replaced by new aggregated features that model the mRNA-miRNA interaction. The proposed subtractive integration method is directly motivated by the inhibition/degradation models of gene expression regulation. The method aggregates mRNA and miRNA expressions by subtracting a proportion of miRNA expression values from their respective target mRNAs. Further, its modification based on singular value decomposition that enables different subtractive weights for different miRNAs is introduced. Both the methods are used to model the outcome or development of myelodysplastic syndrome, a blood cell production disease often progressing to leukemia. The reached results demonstrate that the integration improves classification performance when dealing with mRNA and miRNA features of comparable significance. The proposed methods are available as a part of the web tool miXGENE.
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References
Anděl, M., Kléma, J., Krejčík, Z.: Integrating mRNA and miRNA expressions with interaction knowledge to predict myelodysplastic syndrome. In: Information Technologies - Applications and Theory, Workshop on Bioinformatics in Genomics and Proteomics, ITAT 2013, pp. 48–55 (2013)
Brewster, J.L., Beason, K.B., Eckdahl, T.T., et al.: The microarray revolution: perspectives from educators. Biochem. Mol. Biol. Educ. 32(4), 217–227 (2004)
Croce, C.M.: Causes and consequences of microRNA dysregulation in cancer. Nat. Rev. Genet. 10(10), 704–714 (2009)
Merkerova, M.D., Krejcik, Z., Votavova, H., et al.: Distinctive microRNA expression profiles in CD34+ bone marrow cells from patients with myelodysplastic syndrome. Eur. J. Hum. Genet. 19(3), 313–319 (2011)
Dweep, H., Sticht, C., Pandey, P., et al.: miRWalk - database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J. Biomed. Inform. 44(5), 839–847 (2011)
Eckart, C., Young, G.: The approximation of one matrix by another of lower rank. Psychometrika 1, 211–8 (1936)
Fabian, M.R., Sonenberg, N.: The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat. Struct. Mol. Biol. 19(6), 586–593 (2012)
Guyon, I., Weston, J., Barnhill, S., Vapnik, V.: Gene selection for cancer classification using support vector machines. Mach. Learn. 46, 389–422 (2002)
Holec, M., Gologuzov, V., Kléma, J.: miXGENE tool for learning from heterogeneous gene expression data using prior knowledge. In: Proceedings of the 27th IEEE International Symposium on Computer-Based Medical Systems 2014 (2014) (to appear)
Huang, G.T., Athanassiou, C., Benos, P.V.: mirConnX: condition-specific mRNA-microRNA network integrator. Nucleic Acids Res. 39, W416–W423 (2011). Web Server issue
Joachims, T.: Text categorization with support vector machines: learning with many relevant features. In: Nédellec, C., Rouveirol, C. (eds.) ECML 1998. LNCS, vol. 1398. Springer, Heidelberg (1998)
Kim, D., Shin, H., Song, Y.S., et al.: Synergistic effect of different levels of genomic data for cancer clinical outcome prediction. J. Biomed. Inform. 45(6), 1191–1198 (2012)
Kozomara, A., Griffiths-Jones, S.: miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39, 152–157 (2011). Database-Issue
Krek, A., Grün, D., Poy, M.N., et al.: Combinatorial microRNA target predictions. Nat. Genet. 37(5), 495–500 (2005)
Lanza, G., Ferracin, M., Gafà, R., et al.: mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol. Cancer 6, 54 (2007)
Lee, R.C., Feinbaum, R.L., Ambros, V.: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75(5), 843–854 (1993)
Lewis, B.P., Shih, I.H.H., et al.: Prediction of mammalian microRNA targets. Cell 115(7), 787–798 (2003)
Li, W., Zhang, S.H., et al.: Identifying multi-layer gene regulatory modules from multi-dimensional genomic data. Bioinformatics 28(19), 2458–66 (2012)
Morin, R., Bainbridge, M., Fejes, A., et al.: Profiling the HeLa S3 transcriptome using randomly primed cDNA and massively parallel short-read sequencing. BioTechniques 45(1), 81–94 (2008)
Peng, X., Li, Y., Walters, K.A., et al.: Computational identification of hepatitis C virus associated microRNA-mRNA regulatory modules in human livers. BMC Genomics 10(1), 373 (2009)
Pollack, J.R., Sørlie, T., Perou, C.M., et al.: Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. Proc. Natl. Acad. Sci. USA 99(20), 12963–12968 (2002)
Rhyasen, G.W., Starczynowski, D.T.: Deregulation of microRNAs in myelodysplastic syndrome. Leukemia 26(1), 13–22 (2012)
Sayed, D., Abdellatif, M.: MicroRNAs in development and disease. Physiol. Rev. 91(3), 827–887 (2011)
Smith, T.F., Waterman, M.S.: Identification of common molecular subsequences. J. Mol. Biol. 147(1), 195–197 (1981)
Stranger, B.E., Forrest, M.S., Dunning, M., et al.: Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315(5813), 848–853 (2007)
Tan Gana, N.H., Victoriano, A.F., Okamoto, T.: Evaluation of online miRNA resources for biomedical applications. Genes Cells 17(1), 11–27 (2012)
Tran, D.H., Satou, K., Ho, T.B.: Finding microRNA regulatory modules in human genome using rule induction. BMC Bioinform. 9(12), S5 (2008)
Vašíková, A., Běličková, M., Budinská, E., et al.: A distinct expression of various gene subsets in cd34+ cells from patients with early and advanced myelodysplastic syndrome. Leuk. Res. 34(12), 1566–1572 (2010)
Wang, X., Naqa, I.M.E.: Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 24(3), 325–332 (2008)
Witten, D.M., Tibshirani, R.J.: Extensions of sparse canonical correlation analysis with applications to genomic data. Stat. Appl. Genet. Mol. Biol. 8(1), 28 (2009)
Zhang, S.H., Li, Q., et al.: A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules. Bioinformatics 27(13), 401–409 (2011)
Acknowledgements
This research was supported by the grants NT14539 and NT1 4377 of the Ministry of Health of the Czech Republic.
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Kléma, J., Zahálka, J., Anděl, M., Krejčík, Z. (2015). Interaction-Based Aggregation of mRNA and miRNA Expression Profiles to Differentiate Myelodysplastic Syndrome. In: Plantier, G., Schultz, T., Fred, A., Gamboa, H. (eds) Biomedical Engineering Systems and Technologies. BIOSTEC 2014. Communications in Computer and Information Science, vol 511. Springer, Cham. https://doi.org/10.1007/978-3-319-26129-4_11
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