ArticleGenome biology2022
Dynamic rewiring of biological activity across genotype and lineage revealed by context-dependent functional interactions.
Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- CLAMP: predicting specific protein-mediated chromatin loops in diverse species with a chromatin accessibility language model.Genome biology · 2026Article
- Quantifying pathway perturbations based on gene network rewiring in sepsis progression toward death or survival.Frontiers in bioinformatics · 2026Article
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- On knowing a gene: A distributional hypothesis of gene function.Cell systems · 2024Review
- Cofitness network connectivity determines a fuzzy essential zone in open bacterial pangenome.mLife · 2024Article
- Prediction of cancer driver genes and mutations: the potential of integrative computational frameworks.Briefings in bioinformatics · 2024Review
- Robust, scalable, and informative clustering for diverse biological networks.Genome biology · 2023Article
- Article
- Optimized whole-genome CRISPR interference screens identify ARID1A-dependent growth regulators in human induced pluripotent stem cells.Stem cell reports · 2023Article
- Comparative landscape of genetic dependencies in human and chimpanzee stem cells.bioRxiv : the preprint server for biology · 2023Article
- Optimal construction of a functional interaction network from pooled library CRISPR fitness screens.BMC bioinformatics · 2022Article
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCoessentiality networks derived from CRISPR screens in cell lines provide a powerful framework for identifying functional modules in the cell and for inferring the roles of uncharacterized genes. However, these networks integrate signal across all underlying data and can mask strong interactions that occur in only a subset of the cell lines analyzed.
resultsHere, we decipher dynamic functional interactions by identifying significant cellular contexts, primarily by oncogenic mutation, lineage, and tumor type, and discovering coessentiality relationships that depend on these contexts. We recapitulate well-known gene-context interactions such as oncogene-mutation, paralog buffering, and tissue-specific essential genes, show how mutation rewires known signal transduction pathways, including RAS/RAF and IGF1R-PIK3CA, and illustrate the implications for drug targeting. We further demonstrate how context-dependent functional interactions can elucidate lineage-specific gene function, as illustrated by the maturation of proreceptors IGF1R and MET by proteases FURIN and CPD.
conclusionsThis approach advances our understanding of context-dependent interactions and how they can be gleaned from these data. We provide an online resource to explore these context-dependent interactions at diffnet.hart-lab.org.
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Registered trials
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.