Title: Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.
Authors: Shen, John Paul; Zhao, Dongxin; Sasik, Roman; Luebeck, Jens; Birmingham, Amanda; Bojorquez-Gomez, Ana; Licon, Katherine; Klepper, Kristin; Pekin, Daniel; Beckett, Alex N; Sanchez, Kyle Salinas; Thomas, Alex; Kuo, Chih-Chung; Du, Dan; Roguev, Assen; Lewis, Nathan E; Chang, Aaron N; Kreisberg, Jason F; Krogan, Nevan; Qi, Lei; Ideker, Trey; Mali, Prashant
Published In Nat Methods, (2017 Jun)
Abstract: We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies.
PubMed ID: 28319113
MeSH Terms: A549 Cells; Cell Line, Tumor; Chromosome Mapping/methods*; Clustered Regularly Interspaced Short Palindromic Repeats/genetics*; Combinatorial Chemistry Techniques*; Epistasis, Genetic/genetics*; HeLa Cells; High-Throughput Nucleotide Sequencing; Humans; Neoplasm Proteins/genetics*