The COVID-19 Drug and Gene Set Library

Maxim V. Kuleshov, Daniel J. Stein, Daniel J.B. Clarke, Eryk Kropiwnicki, Kathleen M. Jagodnik, Alon Bartal, John E. Evangelista, Jason Hom, Minxuan Cheng, Allison Bailey, Abigail Zhou, Laura B. Ferguson, Alexander Lachmann, Avi Ma'ayan

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

In a short period, many research publications that report sets of experimentally validated drugs as potential COVID-19 therapies have emerged. To organize this accumulating knowledge, we developed the COVID-19 Drug and Gene Set Library (https://amp.pharm.mssm.edu/covid19/), a collection of drug and gene sets related to COVID-19 research from multiple sources. The platform enables users to view, download, analyze, visualize, and contribute drug and gene sets related to COVID-19 research. To evaluate the content of the library, we compared the results from six in vitro drug screens for COVID-19 repurposing candidates. Surprisingly, we observe low overlap across screens while highlighting overlapping candidates that should receive more attention as potential therapeutics for COVID-19. Overall, the COVID-19 Drug and Gene Set Library can be used to identify community consensus, make researchers and clinicians aware of new potential therapies, enable machine-learning applications, and facilitate the research community to work together toward a cure. The COVID-19 pandemic requires rapid response by the research community to develop vaccines and therapeutics. While the development of vaccines may take years, drug repurposing can offer pandemic mitigation much quicker. In vitro drug screening is the first step toward identifying and prioritizing potential safe therapeutics for COVID-19. However, these screens are done by different laboratories across the world using different methods. As a result, these screens produce different lists of hits. Here, we attempted to consolidate the results from these drug screens to find out whether consensus emerges. In addition, we utilized machine-learning methods to further predict and prioritize the validity of the hits from these drug screens. Such analysis identified molecular mechanisms that may explain how some of these drugs interfere with viral replication inside human cells. As more SARS-CoV-2 drug screens are published, a clearer picture of the most promising drug candidates is expected to emerge. Kuleshov et al. developed a web-based platform that collects and presents drug and gene sets related to COVID-19 research. Analysis of the results from six in vitro drug screens by comparing the overlap among these screens shows that there is some unexpected overlap among them. The authors also use the hits from these screens to develop a machine-learning classifier that further prioritizes the hits and identifies a pharmacological theme that is shared among several hits.

Original languageEnglish
Article number100090
JournalPatterns
Volume1
Issue number6
DOIs
StatePublished - 11 Sep 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 The Authors

Funding

We would like to thank Akira Mitsui, Russ Altman, Anne Carpenter, Pedro Bellester, and Tudor Oprea for contributing information about missing publications and contributing drug and gene sets to the library. This project is partially funded by NIH U54HL127624 and U24CA224260 awarded to A.M. and NIH grants U24AA025479 and F32AA028148 supporting the work of L.B.F.

FundersFunder number
National Institutes of HealthU24CA224260, F32AA028148, U54HL127624, U24AA025479

    Keywords

    • COVID-19
    • DSML 3: Development/Pre-production: Data science output has been rolled out/validated across multiple domains/problems
    • SARS-CoV-2
    • crowdsourcing
    • drug set enrichment analysis
    • drugs
    • gene set enrichment analysis
    • in vitro screens

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