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

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Deciphering how genes interact within human cells is essential for understanding their functional wiring and for developing 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 for systematically exploring the roles of genes and their functional connections in human cell lines.

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Billmann, Maximilian; Costanzo, Michael; Zhang, Xiang; Hassan, Arshia Z.; Rahman, Mahfuzur; Brown, Kevin R.; Chan, Katherine S.; Tong, Amy Hin Yan; Po (2026). Global genetic interaction network of a human cell maps conserved principles and informs functional interpretation of gene co-essentiality profiles. Cell, (), -. DOI: 10.1016/j.cell.2026.03.044

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Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

# metadata.dc.title[].value
Global genetic interaction network of a human cell maps conserved principles and informs functional interpretation of gene co-essentiality profiles