[March 15, 2026] In their August 2025 PNAS article “Patient stratification reveals the molecular basis of disease co-occurrences”, Urda-García et al. describe a transcriptomics-based framework to model disease comorbidity using RNA-seq data from 45 human diseases. Disease Similarity and Stratified Similarity Networks were constructed from correlated gene expression profiles, recovering 64% of known epidemiological disease co-occurrences. Reactome was used as the pathway knowledgebase to aggregate and compare dysregulated biological processes across diseases, enabling pathway-level similarity analysis and revealing immune system pathways as a dominant contributor to disease co-occurrence. The study shows that patient stratification combined with Reactome-based pathway interpretation improves resolution of molecular relationships underlying clinical comorbidity.

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