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Applications of machine learning in drug discovery and development

Nature Reviews Drug Discovery volume 18, pages 463–477 (2019)Cite this article

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Abstract

Drug discovery and development pipelines are long, complex and depend on numerous factors. Machine learning (ML) approaches provide a set of tools that can improve discovery and decision making for well-specified questions with abundant, high-quality data. Opportunities to apply ML occur in all stages of drug discovery. Examples include target validation, identification of prognostic biomarkers and analysis of digital pathology data in clinical trials. Applications have ranged in context and methodology, with some approaches yielding accurate predictions and insights. The challenges of applying ML lie primarily with the lack of interpretability and repeatability of ML-generated results, which may limit their application. In all areas, systematic and comprehensive high-dimensional data still need to be generated. With ongoing efforts to tackle these issues, as well as increasing awareness of the factors needed to validate ML approaches, the application of ML can promote data-driven decision making and has the potential to speed up the process and reduce failure rates in drug discovery and development.

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Fig. 1: Machine learning applications in the drug discovery pipeline and their required data characteristics.
Fig. 2: Machine learning tools and their drug discovery applications.
Fig. 3: The challenges of compound structure representation in machine learning models.
Fig. 4: Utilizing predictive biomarkers to support drug discovery and development.
Fig. 5: Computational pathology tasks for machine learning applications.

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Acknowledgements

The authors thank E. Birney and E. Papa for helpful comments, M. Segler for contributing to the small-molecule optimization subsection and A. Janowczyk for providing the pathology images in Figure 4.

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Authors and Affiliations

  1. European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK

    Jessica Vamathevan, Dominic Clark & Edgardo Ferran

  2. Technical University of Dortmund, Dortmund, Germany

    Paul Czodrowski

  3. Open Targets and European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK

    Ian Dunham & Michaela Spitzer

  4. Bristol-Myers Squibb, Princeton, NJ, USA

    George Lee

  5. Takeda Pharmaceuticals International Co., Cambridge, MA, USA

    Bin Li

  6. Case Western Reserve University, Cleveland, OH, USA

    Anant Madabhushi

  7. Louis Stokes Cleveland Veterans Affair Medical Center, Cleveland, OH, USA

    Anant Madabhushi

  8. EMD Serono R&D Institute, Billerica, MA, USA

    Parantu Shah

  9. Pfizer Worldwide Research and Development, Cambridge, MA, USA

    Shanrong Zhao

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  1. Jessica Vamathevan
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Correspondence to Jessica Vamathevan.

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Related links

DeepChem: https://www.deepchem.io/

DREAM Challenges: http://dreamchallenges.org/

TensorFlow: https://www.tensorflow.org/

Glossary

Graphical processing units

(GPUs). Processors designed to accelerate the rendering of graphics and that can handle tens of thousands of operations per cycle.

Central processing units

(CPUs). Processors designed to solve every computational problem in a general fashion and that can handle tens of operations per cycle. The cache and memory are designed to be optimal for any general programming problem.

Tensor processing units

(TPUs). Co-processors manufactured by Google that are designed to accelerate deep learning tasks developed using TensorFlow (a programming framework) and can handle up to 128,000 operations per cycle.

Support vector machine (SVM) classifier

A method that performs classification tasks by constructing separating lines to distinguish between objects with different class memberships in a multi-dimensional space.

CLIP–seq

Ultraviolet crosslinking immunoprecipitation (CLIP) followed by RNA sequencing to identify all RNA species bound by a protein of interest. This method can be used to map RNA protein binding sites or RNA modification sites on a genome-wide scale.

Heuristic method

A function that calculates the approximate cost of a problem (or ranks alternatives).

Chemical fingerprint

A concept used in chemical informatics to compare molecules with each other. The structure of a molecule is encoded in a series of binary digits (bits) that represent the presence or absence of particular substructures in the molecule.

Simplified molecular input line entry system (SMILES)

A line notation for entering and representing molecules and reactions; for example, carbon dioxide is represented as O = C = O.

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Vamathevan, J., Clark, D., Czodrowski, P. et al. Applications of machine learning in drug discovery and development. Nat Rev Drug Discov 18, 463–477 (2019). https://doi.org/10.1038/s41573-019-0024-5

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