phyloDS: phylogeny-aware differential splicing across species, beyond reference annotations
Abstract
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 orthologous splice junctions on multiple sequence alignments of one-to-one orthologous genes, tests their differential usage with a regularized Ornstein--Uhlenbeck model, and cross-validates detected shifts against splice-site predictions made from genomic sequence alone. Applied to primate brain and rodent heart transcriptomes, phyloDS recovered up to 2.9-fold more shared orthologous splice junctions than a reference-based strategy and kept type~I error near nominal where competing methods inflate it more than two-fold. It identified 234 and 502 differentially used orthologous splice junctions in hominoids and mole-rats (86 and 141 unannotated), revealing a mitochondrial and contractile splicing signature in mole-rats.
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BibTeX
@misc{liehrmann2026phylods,
title = {{phyloDS: phylogeny-aware differential splicing across species, beyond reference annotations}},
author = {Arnaud Liehrmann and Louis Carrel Billiard and Paul Bastide and Mélina Gallopin and Hugues Richard and Élodie Laine},
howpublished = {HAL},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756841},
url = {https://hal.sorbonne-universite.fr/hal-05837768v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - phyloDS: phylogeny-aware differential splicing across species, beyond reference annotations
AU - Arnaud Liehrmann
AU - Louis Carrel Billiard
AU - Paul Bastide
AU - Mélina Gallopin
AU - Hugues Richard
AU - Élodie Laine
PY - 2026
DA - 2026/10/05
PB - HAL
DO - 10.64898/2026.10.05.756841
UR - https://hal.sorbonne-universite.fr/hal-05837768v1
AB - 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 orthologous splice junctions on multiple sequence alignments of one-to-one orthologous genes, tests their differential usage with a regularized Ornstein--Uhlenbeck model, and cross-validates detected shifts against splice-site predictions made from genomic sequence alone. Applied to primate brain and rodent heart transcriptomes, phyloDS recovered up to 2.9-fold more shared orthologous splice junctions than a reference-based strategy and kept type~I error near nominal where competing methods inflate it more than two-fold. It identified 234 and 502 differentially used orthologous splice junctions in hominoids and mole-rats (86 and 141 unannotated), revealing a mitochondrial and contractile splicing signature in mole-rats.
ER -