PT  - JOURNAL ARTICLE
AU  - Benedikt Rauscher
AU  - Florian Heigwer
AU  - Luisa Henkel
AU  - Thomas Hielscher
AU  - Michael Boutros
TI  - A Map of Genetic Interactions in Cancer Cells
AID  - 10.1101/120964
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 120964
4099  - http://biorxiv.org/content/early/2017/03/27/120964.short
4100  - http://biorxiv.org/content/early/2017/03/27/120964.full
AB  - Cancer genomes often harbor hundreds of molecular aberrations. Such genetic variants can be drivers or passengers of tumorigenesis and, as a side effect, create new vulnerabilities for potential therapeutic exploitation. To systematically identify genotypedependent vulnerabilities and synthetic lethal interactions, forward genetic screens in different genetic backgrounds have been conducted. Here, we extended genetic interaction network analysis approaches that were established for model organisms to integrate and analyze data from 83 CRISPR/Cas9 screens in human cancer cell lines. We integrated functional data with information on loss-of-function variants to explore the relationships of more than 2.2 million gene-gene combinations. In addition to known gene-gene dependencies, our analysis identified new genotype-specific vulnerabilities of cancer cells. By clustering genes with similar genetic interaction profiles, we drew the largest map of genetic interactions in a cancer cell to date. This approach is scalable and highlights how diverse genetic screens can be integrated to comprehensively build maps of genetic interactions in cancer.