Structured cross-omics interaction discovery with a triple-graph model

Multi-omics analyses often yield fragmented pairwise associations that obscure coordinated relationships among molecular features. We developed TriGer, a triple-graph framework that identifies many-to-many cross-omics modules by combining cross-layer associations with dependency structures within each layer. In simulations with sparse or nested signals, TriGer recovered planted modules while balancing sensitivity and specificity. In inflammatory bowel disease, it identified subtype-associated metabolite–transcript modules; in colorectal cancer, it identified genus–metabolite modules whose organization was attenuated in cancer. TriGer provides an interpretable approach for studying coordinated cross-omics structure in high-dimensional molecular data.