{
  "id": 14080774,
  "title": "phyloDS: phylogeny-aware differential splicing across species, beyond reference annotations",
  "url": "https://urgent.news/2026/10/12/phylods-phylogeny-aware-differential-splicing-across-species-beyond",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-12T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756841v1?rss=1"
  },
  "original_language": "en",
  "account": "Alternative splicing varies widely between species, but its comparative analysis has lagged significantly behind that of gene expression analysis. Traditional methods define junction orthology using a single reference genome, treat species as independent samples, and rarely rely on sequence-level evidence to substantiate detected shifts. To address these limitations, researchers have developed phyloDS, an RNA-seq-driven framework.\n\nThe phyloDS approach identifies orthologous splice junctions by analyzing multiple sequence alignments of one-to-one orthologous genes. It then tests the differential usage of these junctions with a regularized Ornstein-Uhlenbeck model. Crucially, phyloDS cross-validates its findings against splice-site predictions generated solely from genomic sequence data, providing a more robust analysis.\n\nWhen applied to primate brain and rodent heart transcriptomes, phyloDS demonstrated its effectiveness. It uncovered up to 2.9 times more shared orthologous splice junctions compared to a reference-based strategy, maintaining type I error rates close to nominal values where competing methods inflated this rate by over two-fold. Furthermore, phyloDS identified 234 and 502 differently used orthologous splice junctions in hominoids and mole-rats, respectively. These findings include 86 and 141 previously unannotated junctions, revealing unique mitochondrial and contractile splicing signatures in mole-rats.",
  "summary": "Alternative splicing diverges rapidly between species, yet its comparative analysis lags far behind that of gene expression: junction orthology is defined on a single reference genome, species are treated as independent samples, and detected shifts are rarely grounded in sequence-level evidence. We present phyloDS, an RNA-seq--driven framework that resolves all three limitations. phyloDS defines…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}