The Dark Regulome: Disentangling Predictability from Regulation in Genomic Foundation Models

In three linesStudy of genomic foundation models to identify regulatory elements in the dark genome (dark regulome) of gliomas. Authors separate sequence predictability from actual regulation via residualization-permutation across three models (Caduceus-Ph, HyenaDNA, Enformer). Results: 10kb proximal regulatory horizon, 3.3× enrichment in brain eQTLs, but LM-derived hierarchy non-reproducible.

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