AI Article Synopsis
- * The researchers used a novel approach combining two different Cas9 proteins to simultaneously activate and delete genes in K562 leukemia cells, allowing them to analyze interactions between gene pairs.
- * Their analysis of over 100,000 gene pairs led to the creation of a directional dependency network, connecting lesser-known genes to established pathways and suggesting potential targets for therapy.
Article Abstract
Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair. Based on the results from over 100,000 perturbed gene pairs, we reconstruct a directional dependency network for human K562 leukemia cells and demonstrate how our approach allows the determination of directionality in activating genetic interactions. Our interaction network connects previously uncharacterized genes to well-studied pathways and identifies targets relevant for therapeutic intervention.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072461 | PMC |
| http://dx.doi.org/10.1038/nbt.4062 | DOI Listing |
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