{
  "abstract": "IntroductionHuman endogenous retroviruses (HERVs) are increasingly recognized as sources of tumor-associated antigens and potential targets for cellular immunotherapy. However, their repetitive sequences and noncanonical splicing patterns complicate accurate transcript annotation using common short-read RNA sequencing. This study aimed to improve HERV transcriptome annotation using long-read RNA sequencing.MethodsWe developed a bioinformatics workflow for comprehensive annotation of HERV expression using long-read RNA sequencing, with validation using short-read RNA sequencing. We applied this workflow to ERVE-4, a HERV element previously shown to be selectively expressed in clear cell renal cell carcinoma (ccRCC) and to encode immunogenic peptides currently under clinical investigation as targets for cellular immunotherapy.ResultsLong-read sequencing captured full-length HERV transcripts, improved mapping across repetitive regions, and enabled reconstruction of HERV isoforms. The workflow identified hundreds of HERV loci in long-read datasets absent from corresponding short-read annotations. Analysis of ERVE-4 revealed previously uncharacterized isoforms, whose expression was validated across multiple ccRCC tumors using RT-dPCR.DiscussionLong-read RNA sequencing improves the resolution and completeness of HERV transcriptome annotation. Novel ERVE-4 isoforms substantially expand the known antigenic coding potential of ERVE-4 possibly implying discovery of novel peptide targets for immunotherapy in ccRCC.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Elena A. Cherkasova"
    },
    {
      "name": "Thomas Hill"
    },
    {
      "name": "Stefan Barisic"
    },
    {
      "name": "Long Chen"
    },
    {
      "name": "Jamie Diemer"
    },
    {
      "name": "Neelam Redekar"
    },
    {
      "name": "Richard W. Childs"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bq3cbpfk92mx5.bib",
  "cited_by": 0,
  "doi": "10.3389/fmolb.2026.1941192",
  "fulltext_url": null,
  "id": "bq3cbpfk92mx5",
  "issns": [
    "2296-889X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fmolb.2026.1941192",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biochemistry/general"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bq3cbpfk92mx5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.3389/fmolb.2026.1941192",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fmolb.2026.1941192"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Protein Structure and Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Long-read RNA sequencing reveals full-length HERV transcripts and novel ERVE-4 isoforms with potential immunotherapeutic relevance in clear cell renal cell carcinoma",
  "title_text": "Long-read RNA sequencing reveals full-length HERV transcripts and novel ERVE-4 isoforms with potential immunotherapeutic relevance in clear cell renal cell carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T00:20:30Z",
  "url": "https://research.draconitic.com/paper/bq3cbpfk92mx5",
  "venue": "Frontiers in Molecular Biosciences",
  "versions": []
}