{
  "abstract": "Perturb-seq uses multiple guides per target as replicates, but off-target effects can bias target-level estimates even with efficient target perturbation. We present PETRO, which recovers the on-target perturbation effect while allowing, for each outcome, an unknown minority of guides to have arbitrary off-target effects. Across CRISPRa and CRISPRi datasets, sequence-associated off-target bias persisted after pooling cells across guides and nearly doubled in one CRISPRa dataset after a published guide filter. PETRO largely removed this bias and reduced transmission of effects from independently flagged promiscuous guides. In simulations, PETRO nearly matched pooling in power without off-target effects; with off-target effects, pooling remained biased as cell numbers increased, whereas PETRO recovered the on-target perturbation effect. In cortical Perturb-seq, most ZNF219 pathway enrichments from pooling rested on one guide and did not survive majority-supported aggregation, unlike those for targets with concordant guides. PETRO enables robust target-level Perturb-seq analysis from replicate-guide agreement.",
  "abstract_shown": true,
  "affiliations": [
    "University of Wisconsin-Madison"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Z. Sun"
    },
    {
      "name": "H. Kang"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Keles"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eg9janpj8tees.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.15.759256",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759256v1.full",
  "id": "eg9janpj8tees",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759256v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "1312|CRISPR and Genetic Engineering"
    ]
  ],
  "openalex": "W7223147893",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759256v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/eg9janpj8tees.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:55Z",
      "native_id": "10.64898/2026.10.15.759256",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759256v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "PETRO enables robust estimation of on-target perturbation effects in Perturb-seq",
  "title_text": "PETRO enables robust estimation of on-target perturbation effects in Perturb-seq",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:55Z",
  "url": "https://research.draconitic.com/paper/eg9janpj8tees",
  "venue": "bioRxiv",
  "versions": []
}