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MethNet: a robust approach to identify regulatory hubs and their distal targets in cancer [Perturb-seq]

ABSTRACT: We present MethNet, a pipeline that integrates large-scale DNA methylation and gene expression data across multiple cancers, to uncover novel cis regulatory elements (CREs) in a 1Mb region around every promoter in the genome. MethNet identifies highly ranked CREs, referred to as ‘hubs’, which contribute to the regulation of multiple genes and strongly affect patient survival. Promoter-capture Hi-C confirmed that highly ranked associations involve physical interactions between CREs and their gene targets, and CRISPRi based scRNA Perturb-seq validated the functional impact of CREs. Thus, MethNet represents a valuable resource for unraveling complex mechanisms underlying gene expression, and for prioritizing the verification of predicted non-coding disease hotspots.

ORGANISM(S): Homo sapiens

PROVIDER: GSE236304 | GEO | 2024/01/01

REPOSITORIES: GEO

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