{
  "abstract": "Linking genetic variants to their functional consequences at scale remains a major challenge in human genetics. Perturb-seq is limited in the variants it can install, while prime editing has largely been restricted to simpler mechanistic readouts. Here, we introduce prime editing perturb-seq (PEP-seq), which links programmed mutations to transcriptomic states. We designed 2,164 prime editing guides targeting common expression quantitative trait loci (eQTLs), premature termination codons, and position-matched synonymous controls, generating 749,110 time-resolved single-cell transcriptomes. PEP-seq precisely detected nonsense-mediated decay, while probe-based junction measurements suggested depletion of mature RNAs. For eQTLs, a locus-size-corrected specificity metric showed that the intended target was frequently the most affected transcript within a 1 Mb window, with effects also associated with open chromatin near the edit site. These results establish PEP-seq as a scalable platform for direct, endogenous variant-to-function mapping.",
  "abstract_shown": true,
  "affiliations": [
    "Relation Therapeutics"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "J. De Jonghe"
    },
    {
      "name": "M. Armas Reyes"
    },
    {
      "name": "C. Jamieson"
    },
    {
      "name": "J. B. Christensen"
    },
    {
      "name": "J. W. Opzoomer"
    },
    {
      "affs": [
        0
      ],
      "name": "J. P. Taylor-King"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dk9dm0ky3tqk4.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.762453",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762453v1.full",
  "id": "dk9dm0ky3tqk4",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762453v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762453v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dk9dm0ky3tqk4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:18Z",
      "native_id": "10.64898/2026.10.28.762453",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762453v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Scalable variant-to-function screens using prime editing perturb-seq",
  "title_text": "Scalable variant-to-function screens using prime editing perturb-seq",
  "type": "preprint",
  "updated_at": "2026-10-30T12:30:18Z",
  "url": "https://research.draconitic.com/paper/dk9dm0ky3tqk4",
  "venue": "bioRxiv",
  "versions": []
}