{
  "abstract": "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. An initial production run suggested ESM-2 retains higher-order epistatic information less well than lower-order information ($Δ_{\\mathrm{HO-LO}}=-0.107$). An independent replication of the complete measurement grid, under matched GPU hardware and identical critic seeds, substantially reduced this contrast ($Δ_{\\mathrm{HO-LO}}=-0.017$), and its sign was unstable across otherwise-defensible evaluation-pairing choices applied to the same trained critics ($-0.011$ to $+0.015$). We therefore do not currently have robust evidence that ESM-2 selectively loses higher-order epistatic information, nor that retention is equal across orders; the directional question remains open. The measurement protocol itself, including its documented removal of a positional-subset shortcut in pooled critics, remains validated and is unaffected by this finding. ORBIT-FMIB is offered as a diagnostic framework for probing interaction structure in protein foundation models; this study's own replication result illustrates why such probing requires adequately-powered reproducibility checks before its output is treated as a biological finding.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2610.00672",
  "author_total": 3,
  "authors": [
    {
      "name": "Maryam Rahimimovassagh"
    },
    {
      "name": "Ivan Garibay"
    },
    {
      "name": "Niloofar Yousefi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dhjndrn9v30zz.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2610.00672",
  "fulltext_url": null,
  "id": "dhjndrn9v30zz",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2610.00672",
  "language": null,
  "licence": "LicenseRef-arXiv-nonexclusive-1.0",
  "licence_label": "arXiv licence",
  "licence_source": "article",
  "licence_url": "http://arxiv.org/licenses/nonexclusive-distrib/1.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "cs.LG"
    ],
    [
      "arxiv",
      "q-bio.QM"
    ],
    [
      "openalex",
      "1311|Evolution and Genetic Dynamics"
    ]
  ],
  "openalex": "W7215918475",
  "pdf_url": "https://arxiv.org/pdf/2610.00672",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dhjndrn9v30zz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:08Z",
      "native_id": "2610.00672",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2610.00672"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "arxiv:q-bio.QM",
      "subfield": "bioinformatics"
    }
  ],
  "title": "ORBIT-FMIB: Tracking Order-Resolved Epistatic Information Through ESM-2",
  "title_text": "ORBIT-FMIB: Tracking Order-Resolved Epistatic Information Through ESM-2",
  "type": "preprint",
  "updated_at": "2026-11-06T18:21:04Z",
  "url": "https://research.draconitic.com/paper/dhjndrn9v30zz",
  "venue": "arXiv",
  "versions": []
}