ORBIT-FMIB: Tracking Order-Resolved Epistatic Information Through ESM-2
Protein foundation models support mutation-effect and structural prediction, but predictive performance alone does not reveal which forms of biological interaction information remain accessible through model depth. We ask whether ESM-2 retains higher-order epistatic information as strongly as first- and second-order information across its representation hierarchy, introducing ORBIT-FMIB, a diagnostic framework combining Walsh-based interaction decomposition with subset-conditioned neural dependence estimation. The method is validated on synthetic landscapes with known interaction structure before being applied to the dense four-site GB1 fitness landscape using frozen ESM-2 representations...
| Authors | Maryam Rahimimovassagh, Ivan Garibay, Niloofar Yousefi |
|---|---|
| Primary category | cs.LG |
| Published | 30 September 2026 |
| Last updated at source | 30 September 2026 |
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