{
  "abstract": "Motivation\n\nSingle-cell RNA-seq captures both mature (spliced) and nascent (unspliced) transcripts, yet standard preprocessing collapses these signals into a single expression matrix, obscuring recoverable structure and introducing splicing-dependent artifacts in downstream analysis. We asked whether treating spliced and unspliced counts as distinct feature sets increases recoverable latent structure in unsupervised dimension reduction.Results\n\nAcross four datasets, we applied non-negative matrix factorization to spliced-only, unspliced-only, added, and concatenated representations, estimating the revealable rank, the largest stable rank achieving near-optimal held-out error, by cross-validation. Concatenated representations exceeded the added representation in all four datasets and surpassed both single-modality inputs in three of four, indicating that preserving splicing status exposes additional stable latent programs beyond either modality alone or their sum. Minimal overlap between spliced- and unspliced-derived factors corresponded to modality-specific gene set enrichment consistent with complementary steady-state and nascent regulatory activity. These results establish splicing status as an informative axis of variation and motivate preserving spliced and unspliced layers as first-class features to maximize information recovery.Availability and implementation\n\nThe singlet R package is available at github.com/zdebruine/singlet. Code to reproduce all figures is available at github.com/Arya-86/nmf-spliced-unspliced.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Information Sciences and Technology, Grand Valley State University, Grand Rapids, MI 49504, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Arya Jadhav",
      "orcid": "0009-0006-6704-9804"
    },
    {
      "affs": [
        0
      ],
      "name": "Zachary J DeBruine",
      "orcid": "0000-0003-2234-4827"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/eb044vewxvzje.bib",
  "cited_by": 0,
  "doi": "10.1093/bioadv/vbag263",
  "fulltext_url": "https://europepmc.org/articles/PMC13718436",
  "id": "eb044vewxvzje",
  "issns": [
    "2635-0041"
  ],
  "landing_url": "https://europepmc.org/article/MED/42960177",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/SCI01060"
    ],
    [
      "heading",
      "Gene Regulation"
    ],
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7223292990",
  "pdf_url": "https://europepmc.org/articles/PMC13718436?pdf=render",
  "pmcid": "PMC13718436",
  "pmid": "42960177",
  "published": "2026-10-22",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/eb044vewxvzje.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:50Z",
      "native_id": "MED:42960177",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960177"
    },
    {
      "first_seen": "2026-11-02T12:22:28Z",
      "native_id": "PMC13718436",
      "source": "pmc",
      "url": "https://doi.org/10.1093/bioadv/vbag263"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Joint representation of spliced and unspliced RNA expands information content in single-cell expression data.",
  "title_text": "Joint representation of spliced and unspliced RNA expands information content in single-cell expression data.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:28Z",
  "url": "https://research.draconitic.com/paper/eb044vewxvzje",
  "venue": "Bioinformatics advances",
  "versions": []
}