{
  "abstract": "The expanding catalog of sQTLs from projects like GTEx has established that genetic risk for complex traits is frequently mediated through RNA splicing. Yet it is generally unknown whether disease-associated splice events produce stable, distinct protein isoforms and whether they are functionally consequent. Even the deepest shotgun proteomics efforts only capture a minority of annotated splice events; isoform-specific peptides are systematically under-sampled by nature of being lower abundance and intrinsically harder to detect. Here, we implement a genetics-guided targeted mass spectrometry (MS) strategy to detect splice-derived protein isoforms prioritized by sQTL colocalization. Using internal standard parallel reaction monitoring (IS-PRM), we targeted 288 peptides corresponding to 166 putative BMD-associated isoforms in differentiating osteoprogenitor cells and patient-derived primary mesenchymal stem cells (MSCs). Targeted acquisition increased recovery of isoform-informative peptides relative to conventional DDA, rescued splice events that were undetected or sparsely sampled under global acquisition, and confirmed protein-level expression of genetically prioritized isoforms in clinical material. Together, this work establishes that targeted MS is a useful approach to support validation of protein expression in studies of the genetics of splicing.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Micah D. Lehe",
      "orcid": "0000-0002-3219-6066"
    },
    {
      "name": "Vasilii Pavelko",
      "orcid": "0000-0001-8142-1621"
    },
    {
      "name": "Erin D. Jeffery",
      "orcid": "0000-0001-9511-7719"
    },
    {
      "name": "Vedavathi Madhu",
      "orcid": "0000-0002-8508-7891"
    },
    {
      "name": "Larry D. Mesner"
    },
    {
      "name": "Megan D. Schertzer",
      "orcid": "0000-0003-4997-8221"
    },
    {
      "name": "Abhijit S. Dighe",
      "orcid": "0000-0003-4234-2618"
    },
    {
      "name": "Charles R. Farber",
      "orcid": "0000-0002-6748-4711"
    },
    {
      "name": "Gloria M. Sheynkman",
      "orcid": "0000-0002-4223-9947"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f0jvmjkqk2fkw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.759629",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.759629v1.full",
  "id": "f0jvmjkqk2fkw",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.759629v1",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "systems biology"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.759629v1.full.pdf",
  "pmcid": "PMC13733976",
  "pmid": "42990444",
  "published": "2026-10-28",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/f0jvmjkqk2fkw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:27Z",
      "native_id": "10.64898/2026.10.28.759629",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.759629v1"
    },
    {
      "first_seen": "2026-11-08T12:23:38Z",
      "native_id": "PMC13733976",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.28.759629"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:systems biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Targeted proteomics informed by long-read RNA-sequencing reveals protein isoform expression associated with bone mineral density",
  "title_text": "Targeted proteomics informed by long-read RNA-sequencing reveals protein isoform expression associated with bone mineral density",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:38Z",
  "url": "https://research.draconitic.com/paper/f0jvmjkqk2fkw",
  "venue": "bioRxiv",
  "versions": []
}