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Topological Analysis of Pathway Activation Reveals Molecular Phenotypes in IBD for Precision Stratification and Targeted Therapy
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Precision phenotyping in IBD: Topology-informed gene pathway activation analysis (TopMD) uncovers distinct, biologically relevant molecular phenotypes.
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TNF pathway as a key axis: Topological clustering distinguishes TNF-low and TNF-high phenotypes, with TNF-low predicted to respond better to anti-TNF therapy.
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5-gene predictive panel: Machine learning applied to pathway activation data yields a 5-gene TNF-low signature that accurately predicts treatment response in an independent cohort.
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Translational and trial impact:Pathway activation gene signatures enable low-cost, qPCR-based tools for precision treatment selection, biomarker-enriched trials, and targeting of multiple therapeutic pathways.
