4.7 Review

Deep learning of pharmacogenomics resources: moving towards precision oncology

Journal

BRIEFINGS IN BIOINFORMATICS
Volume 21, Issue 6, Pages 2066-2083

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/bib/bbz144

Keywords

deep learning; precision oncology; pharmacogenomics; cancer; drug discovery

Funding

  1. National Cancer Institute (NCI) Cancer Center Shared Resources (NIH-NCI) [P30CA54174]
  2. National Institutes of Health (NIH) [CTSA 1UL1RR025767-01, R01GM113245]
  3. Cancer Prevention and Research Institute of Texas (CPRIT) [RP160732, RP190346, RR170055]
  4. San Antonio Life Sciences Institute (SALSI Innovation Challenge Award 2016)
  5. San Antonio Life Sciences Institute (SALSI Postdoctoral Research Fellowship)
  6. National Center for Advancing Translational Sciences of the National Institutes of Health TL1 Translational Science Training award [TL1TR002647]
  7. American Association for Cancer Research-AstraZeneca Stimulating Therapeutic Advances through Research Training grant [18-40-12-GORT]

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The recent accumulation of cancer genomic data provides an opportunity to understand how a tumor's genomic characteristics can affect its responses to drugs. This field, called pharmacogenomics, is a key area in the development of precision oncology. Deep learning (DL) methodology has emerged as a powerful technique to characterize and learn from rapidly accumulating pharmacogenomics data. We introduce the fundamentals and typical model architectures of DL. We review the use of DL in classification of cancers and cancer subtypes (diagnosis and treatment stratification of patients), prediction of drug response and drug synergy for individual tumors (treatment prioritization for a patient), drug repositioning and discovery and the study of mechanism/mode of action of treatments. For each topic, we summarize current genomics and pharmacogenomics data resources such as pan-cancer genomics data for cancer cell lines (CCLs) and tumors, and systematic pharmacologic screens of CCLs. By revisiting the published literature, including our in-house analyses, we demonstrate the unprecedented capability of DL enabled by rapid accumulation of data resources to decipher complex drug response patterns, thus potentially improving cancer medicine. Overall, this review provides an in-depth summary of state-of-the-art DL methods and up-to-date pharmacogenomics resources and future opportunities and challenges to realize the goal of precision oncology.

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