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shinyDepMap, a tool to identify targetable cancer genes and their functional connections from Cancer Dependency Map data

Kaoru Shimada, John A. Bachman, Jeremy L. Muhlich, Timothy J. Mitchison

2021eLife89 citationsDOIOpen Access PDF

Abstract

Individual cancers rely on distinct essential genes for their survival. The Cancer Dependency Map (DepMap) is an ongoing project to uncover these gene dependencies in hundreds of cancer cell lines. To make this drug discovery resource more accessible to the scientific community, we built an easy-to-use browser, shinyDepMap (https://labsyspharm.shinyapps.io/depmap). shinyDepMap combines CRISPR and shRNA data to determine, for each gene, the growth reduction caused by knockout/knockdown and the selectivity of this effect across cell lines. The tool also clusters genes with similar dependencies, revealing functional relationships. shinyDepMap can be used to (1) predict the efficacy and selectivity of drugs targeting particular genes; (2) identify maximally sensitive cell lines for testing a drug; (3) target hop, that is, navigate from an undruggable protein with the desired selectivity profile, such as an activated oncogene, to more druggable targets with a similar profile; and (4) identify novel pathways driving cancer cell growth and survival.

Topics & Concepts

DruggabilityCancer cell linesComputational biologyGeneDrug discoveryCRISPRCancerBiologyGene knockdownCancer cellBioinformaticsGeneticsBioinformatics and Genomic NetworksProtein Degradation and InhibitorsCRISPR and Genetic Engineering
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