Journal Article

DKFZ-2018-00238

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Toward an integrated map of genetic interactions in cancer cells.

Rauscher, B. G. (First author)DKFZ* ; Heigwer, F.DKFZ* ; Henkel, L.DKFZ* ; Hielscher, T.DKFZ* ; Voloshanenko, O.DKFZ* ; Boutros, M. (Last author)DKFZ*

2018
EMBO Press Heidelberg

This record in other databases:  

Please use a persistent id in citations: doi: DOI: 10.15252/msb.20177656

Abstract: Cancer genomes often harbor hundreds of molecular aberrations. Such genetic variants can be drivers or passengers of tumorigenesis and create vulnerabilities for potential therapeutic exploitation. To identify genotype-dependent vulnerabilities, forward genetic screens in different genetic backgrounds have been conducted. We devised MINGLE, a computational framework to integrate CRISPR/Cas9 screens originating from different libraries building on approaches pioneered for genetic network discovery in model organisms. We applied this method to integrate and analyze data from 85 CRISPR/Cas9 screens in human cancer cells combining functional data with information on genetic variants to explore more than 2.1 million gene-background relationships. In addition to known dependencies, we identified new genotype-specific vulnerabilities of cancer cells. Experimental validation of predicted vulnerabilities identified GANAB and PRKCSH as new positive regulators of Wnt/β-catenin signaling. By clustering genes with similar genetic interaction profiles, we drew the largest genetic network in cancer cells to date. Our scalable approach highlights how diverse genetic screens can be integrated to systematically build informative maps of genetic interactions in cancer, which can grow dynamically as more data are included.

---

Contributing Institute(s):

1. B110 Signalwege funktionelle Genomik (B110)
2. C060 Biostatistik (C060)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2018

---

Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---