{
  "abstract": "-an interpretable measure derived from entropy-that quantifies the effective number of isoforms per gene based on the full, unfiltered isoform ratio distribution. Calculating perplexity for 124 ENCODE4 PacBio LRS datasets spanning 55 human cell types, we show that it provides intuitive assessments of isoform diversity and captures uncertainty across genes with varying complexity. Perplexity can be calculated at multiple gene regulatory levels-from transcript to protein-to compare how isoform diversity is reduced across stages of gene expression. On average, genes have an ORF-level perplexity of 2.1, indicating production of two distinct protein isoforms. We extended this analysis to evaluate expression variation across tissues and identified 4,593 ORFs across 3,102 genes with moderate to extreme tissue-specificity. We propose perplexity as a consistent, quantitative metric for interpreting isoform diversity across genes, cell types, and disease states. All results are compiled into a community resource to enable cross-study comparisons of novel isoforms.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Computer Science, Columbia University, New York, NY",
    "New York Genome Center, New York, NY",
    "Department of Systems Biology, Columbia University, New York, NY",
    "Life Sciences Department, Barcelona Supercomputing Center (BSC), Barcelona, Catalonia",
    "Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA",
    "Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA",
    "UVA Comprehensive Cancer Center, University of Virginia, Charlottesville, VA",
    "Data Science Institute, Columbia University, New York, NY"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Megan D. Schertzer",
      "orcid": "0000-0003-4997-8221"
    },
    {
      "affs": [
        1
      ],
      "name": "S H Park",
      "orcid": "0009-0008-0933-8602"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiayu Su",
      "orcid": "0000-0002-8997-9272"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Fairlie Reese",
      "orcid": "0000-0002-9240-0102"
    },
    {
      "affs": [
        4,
        5,
        6,
        7,
        1
      ],
      "name": "Gloria M. Sheynkman",
      "orcid": "0000-0002-4223-9947"
    },
    {
      "affs": [
        7,
        0,
        2,
        1
      ],
      "name": "David A. Knowles",
      "orcid": "0000-0002-7408-146X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bqxn3s8egmv1k.bib",
  "cited_by": 9,
  "doi": "10.1186/s13059-026-04260-2",
  "fulltext_url": null,
  "id": "bqxn3s8egmv1k",
  "issns": [
    "1465-6906",
    "1465-6914",
    "1474-7596",
    "1474-760X"
  ],
  "landing_url": "https://doi.org/10.1186/s13059-026-04260-2",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|RNA Research and Splicing"
    ]
  ],
  "openalex": "W4411946888",
  "pdf_url": null,
  "pmcid": "PMC12236620",
  "pmid": "40631152",
  "published": "2026-09-02",
  "publisher": "BioMed Central",
  "ris": "https://research.draconitic.com/paper/bqxn3s8egmv1k.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T13:21:07Z",
      "native_id": "W4411946888",
      "source": "openalex",
      "url": "https://doi.org/10.1186/s13059-026-04260-2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Research and Splicing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Perplexity as a metric for isoform diversity in the human transcriptome",
  "title_text": "Perplexity as a metric for isoform diversity in the human transcriptome",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:07Z",
  "url": "https://research.draconitic.com/paper/bqxn3s8egmv1k",
  "venue": "Genome biology",
  "versions": []
}