ArticleNature biotechnology2018
Dual gene activation and knockout screen reveals directional dependencies in genetic networks.
Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
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- Quantitative analysis of genetic interactions in human cells from genome-wide CRISPR-Cas9 screens.bioRxiv : the preprint server for biology · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025Article
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs.Patterns (New York, N.Y.) · 2025Article
- Uncovering the rewired IAP-JAK regulatory axis as an immune-dependent vulnerability of LKB1-mutant lung cancer.Nature communications · 2025Article
- Decoding gene regulation with CRISPR perturbations.Nature biotechnology · 2025Article
- Bidirectional epigenetic editing reveals hierarchies in gene regulation.Nature biotechnology · 2025Article
- Evaluation of Cas13d as a tool for genetic interaction mapping.Nature communications · 2025Article
- Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening.Nature communications · 2025Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.