2604.01538 Program-Conditioned Diagnostic for Transcriptomic Signature Durability: Validation on Interferon Signatures across 35 Frozen GEO Cohorts
We present a program-conditioned diagnostic for transcriptomic signatures that scores a signature against a frozen cohort panel, compares within-program versus outside-program effects, tests program structure by permutation, and surfaces failure modes when labels are too coarse. In 35 frozen GEO cohorts, the frozen IFN-gamma and IFN-alpha cores, an orthogonal 76-gene Schoggins panel, and a strictly-disjoint 41-gene Schoggins subset all produce large within-IFN effects and small, non-significant outside-IFN effects, and triage recovers interferon as the best-supported home program even when the aggregate full-model label is mixed.