PT  - JOURNAL ARTICLE
AU  - Michael Boettcher
AU  - Ruilin Tian
AU  - James Blau
AU  - Evan Markegard
AU  - David Wu
AU  - Anne Biton
AU  - Noah Zaitlen
AU  - Frank McCormick
AU  - Martin Kampmann
AU  - Michael T. McManus
TI  - Decoding directional genetic dependencies through orthogonal CRISPR/Cas screens
AID  - 10.1101/120170
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 120170
4099  - http://biorxiv.org/content/early/2017/03/25/120170.short
4100  - http://biorxiv.org/content/early/2017/03/25/120170.full
AB  - Genetic interaction studies are a powerful approach to identify functional interactions between genes. This approach can reveal networks of regulatory hubs and connect uncharacterised genes to well-studied pathways. However, this approach has previously been limited to simple gene inactivation studies. Here, we present an orthogonal CRISPR/Cas-mediated genetic interaction approach that allows the systematic activation of one gene while simultaneously knocking out a second gene in the same cell. We have developed this concept into a quantitative and scalable combinatorial screening platform that allows the parallel interrogation of hundreds of thousands of genetic interactions. We demonstrate that the established platform works robustly to uncover genetic interactions in human cancer cells and to interpret the direction of the flow of genetic information.