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A tool for browsing the Cancer Dependency Map reveals functional connections between genes and helps predict the efficacy and selectivity of candidate cancer drugs

View ORCID ProfileKenichi Shimada, Jeremy L Muhlich, Timothy J Mitchison
doi: https://doi.org/10.1101/2019.12.13.874776
Kenichi Shimada
Laboratory of Systems Pharmacology and Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
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  • For correspondence: kenichi_shimada@hms.harvard.edu
Jeremy L Muhlich
Laboratory of Systems Pharmacology and Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
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Timothy J Mitchison
Laboratory of Systems Pharmacology and Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
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Summary

Individual cancers rely on distinct essential genes for their survival. The Cancer Dependency Map (DepMap) is an ongoing project to uncover gene dependency in hundreds of cancer cell lines. DepMap is a powerful drug discovery tool, but can be challenging to use without professional bioinformatics assistance. We combined CRISPR and shRNA screening data from DepMap and built a non-programmer-friendly browser (https://labsyspharm.shinyapps.io/depmap) that reports, for each gene, the growth reduction that can be expected on loss of a gene or inhibition of its action (efficacy) and the selectivity of this effect across cell lines. Cluster analysis revealed proteins that work together in pathways or complexes. This tool can be used to 1) predict the efficacy and selectivity of candidate drugs; 2) identify targets for highly selective drugs; 3) identify maximally sensitive cell lines for testing a drug; 4) target hop, i.e., navigate from an undruggable protein with the desired selectively profile, such as an activated oncogene, to more druggable targets with a similar profile; and 5) identify novel pathways needed for cancer cell growth and survival.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted December 18, 2019.
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A tool for browsing the Cancer Dependency Map reveals functional connections between genes and helps predict the efficacy and selectivity of candidate cancer drugs
Kenichi Shimada, Jeremy L Muhlich, Timothy J Mitchison
bioRxiv 2019.12.13.874776; doi: https://doi.org/10.1101/2019.12.13.874776
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A tool for browsing the Cancer Dependency Map reveals functional connections between genes and helps predict the efficacy and selectivity of candidate cancer drugs
Kenichi Shimada, Jeremy L Muhlich, Timothy J Mitchison
bioRxiv 2019.12.13.874776; doi: https://doi.org/10.1101/2019.12.13.874776

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