{
  "abstract": "The last five-plus years have seen many protein engineering disciplines transformed by advances in machine learning (ML), but the same cannot be said for directed evolution. Reflecting on a previously co-authored perspective, I discuss why I believe this to be the case, arguing that a disconnect between the goals of machine-learning-assisted directed evolution (MLDE) researchers--\"identify an optimal protein\"--and the goals of directed evolution more broadly--\"identify a sufficient protein given time and resource constraints\"--is a principal culprit. As an example, I highlight how nearly all current MLDE methods neglect to account for the cost of DNA synthesis, resulting in strategies that have limited practical applicability regardless of the underlying models' capabilities. I close by discussing recent works that are exceptions to this overarching trend, and emphasize that the last five years of efforts in ML-assisted protein engineering and the prescribed reframe of MLDE objectives need not be mutually exclusive.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": "2609.03046",
  "author_total": 1,
  "authors": [
    {
      "name": "Bruce J. Wittmann"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d2tdrsnz2p7b6.bib",
  "cited_by": 0,
  "doi": "10.48550/arxiv.2609.03046",
  "fulltext_url": null,
  "id": "d2tdrsnz2p7b6",
  "issns": [],
  "landing_url": "https://arxiv.org/abs/2609.03046",
  "language": null,
  "licence": "CC-BY-SA-4.0",
  "licence_label": "CC BY-SA 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by-sa/4.0/",
  "metadata_licence": "CC0-1.0",
  "native_subjects": [
    [
      "arxiv",
      "cs.LG"
    ],
    [
      "arxiv",
      "q-bio.BM"
    ],
    [
      "openalex",
      "1312|Protein Structure and Dynamics"
    ]
  ],
  "openalex": "W7208768273",
  "pdf_url": "https://arxiv.org/pdf/2609.03046",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d2tdrsnz2p7b6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:34:38Z",
      "native_id": "2609.03046",
      "source": "arxiv",
      "url": "https://arxiv.org/abs/2609.03046"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "arxiv:q-bio.BM",
      "subfield": "biophysics"
    }
  ],
  "title": "Advances in Machine Learning for Directed Evolution: A Five-Year Retrospective",
  "title_text": "Advances in Machine Learning for Directed Evolution: A Five-Year Retrospective",
  "type": "preprint",
  "updated_at": "2026-10-30T12:34:38Z",
  "url": "https://research.draconitic.com/paper/d2tdrsnz2p7b6",
  "venue": "arXiv",
  "versions": []
}