Global genetic interaction network of a human cell maps conserved principles and informs functional interpretation of gene co-essentiality profiles
Summary
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
Content
# Global genetic interaction network of a human cell maps conserved principles and informs functional interpretation of gene co-essentiality profiles
*Published: 2026 Apr 27*
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.
DOI: 10.1016/j.cell.2026.03.044