% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Rauscher:132560,
author = {B. G. Rauscher$^*$ and F. Heigwer$^*$ and L. Henkel$^*$ and
T. Hielscher$^*$ and O. Voloshanenko$^*$ and M. Boutros$^*$},
title = {{T}oward an integrated map of genetic interactions in
cancer cells.},
journal = {Molecular systems biology},
volume = {14},
number = {2},
issn = {1744-4292},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DKFZ-2018-00238},
pages = {e7656},
year = {2018},
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.},
cin = {B110 / C060},
ddc = {570},
cid = {I:(DE-He78)B110-20160331 / I:(DE-He78)C060-20160331},
pnm = {312 - Functional and structural genomics (POF3-312)},
pid = {G:(DE-HGF)POF3-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29467179},
pmc = {pmc:PMC5820685},
doi = { DOI: 10.15252/msb.20177656 },
url = {https://inrepo02.dkfz.de/record/132560},
}