The Dark Regulome: Disentangling Predictability from Regulation in Genomic Foundation Models
High-grade gliomas integrate into neural circuits through functional synapses with neurons, raising the question of which noncoding elements shape synaptogenic gene expression in tumor cells. The regulatory program written across the dark genome, what we call the $\textit{dark regulome}$, is the natural substrate to probe, and sequence foundation models offer a zero-shot route through in-silico mutagenesis (ISM); yet likelihood-based scoring is tautologically coupled to local sequence predictability, leaving the regulatory interpretation underdetermined. Across three architecturally distinct foundation models (Caduceus-Ph, HyenaDNA, Enformer) and 30,448 dark genome elements at 92 glioma-r...
| Authors | Chahat Baranwal, Aaditya Baranwal, Lakshya Nitin Tandon |
|---|---|
| Primary category | cs.CL |
| Published | 5 June 2026 |
| Last updated at source | 14 June 2026 |
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