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A statistical physics approach to integrating multi-omics data for disease-module detection

Cell Rep Methods. 2025 Sep 19:101183. doi: 10.1016/j.crmeth.2025.101183. Online ahead of print.

ABSTRACT

Genes associated with the same disease frequently engage in mutual biological interactions, e.g., perturbation within a specific neighborhood in the molecular interactome, often referred to as the disease module. This has propelled the advancement of network-based approaches toward elucidating the molecular bases of human diseases. Although many computational methods have been developed to integrate the molecular interactome and omics profiles to extract such context-dependent disease modules, approaches that leverage multi-omics for disease-module detection are still lacking. Here, we developed a statistical physics approach based on the random-field O(n) model (RFOnM) to fill this gap. We applied the RFOnM approach to integrate gene-expression data and genome-wide association studies or mRNA data and DNA methylation for several complex diseases with the human interactome. We found that the RFOnM approach outperforms existing single omics methods in most of the complex diseases considered in this study.

PMID:40975055 | DOI:10.1016/j.crmeth.2025.101183

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Systems-level design principles of metabolic rewiring in an animal

Nature, Published online: 26 February 2025; doi:10.1038/s41586-025-08636-5

Systems-level Worm Perturb-Seq of metabolic genes reveals design principles of transcriptional metabolic rewiring, many of which can be explained by a compensation–repression model.

Deep whole-genome analysis of 494 hepatocellular carcinomas

Nature, Published online: 14 February 2024; doi:10.1038/s41586-024-07054-3

The Chinese Liver Cancer Atlas project depicts a panoramic genomic landscape of hepatocellular carcinoma, covering candidate coding and non-coding drivers, mutational signatures, extrachromosomal circular DNA, subclonal catastrophic events and detailed evolutionary history.
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