Global genetic interaction network of a human cell maps conserved principles and informs functional interpretation of gene co-essentiality profiles. Billmann et al.

Published: 18 June 2026| Version 2 | DOI: 10.17632/bpcpfns6vb.2
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Description

Deciphering how genes interact within human cells is essential for understanding their functional wiring and the development of targeted therapeutic strategies. In this study, we present a genome-scale map of genetic interactions in the human haploid cell line HAP1, based on CRISPR-based perturbation of ~ 4 million gene pairs. The resulting network comprises ~89,000 high-confidence gene-gene interactions, organizing genes into hierarchical modules corresponding to protein complexes and pathways, biological processes, and cellular compartments, mirroring principles observed in yeast and highlighting the functional architecture of a human cell. This large-scale genetic network complements the DepMap gene co-essentiality network by capturing unique functional information, uncovering roles of previously uncharacterized genes, and identifying molecular determinants of cancer cell line-specific genetic dependencies. This study presents a general data-driven strategy analysis for systematically exploring the roles of genes and their functional connections in human cell lines.

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Genetics, Biological Network

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