ArticlemedRxiv : the preprint server for health sciences2025
Long-read transcriptome analysis using IsoRanker for identifying pathogenic variants in Mendelian conditions.
Yong-Han Hank Cheng, Adriana E Sedeño-Cortés, Jane E Ranchalis, Katherine M Munson, Mitchell R Vollger, Elsa Balton, Casie A Genetti, Undiagnosed Diseases Network, Genomics Research to Elucidate the Genetics of Rare Diseases consortium, University of Washington Center for Rare Diseases Research, Monica H Wojcik, Alan H Beggs and 10 more
Abstract readPreprint
In one paragraphArticle in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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0citing papers in PubMed
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What it found
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2 · The registryThe trial behind it
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3 · Its place in the literatureWho cites it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
20 authors.
Yong-Han Hank ChengDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0001-7686-0697 Adriana E Sedeño-CortésDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0001-7959-8970 Jane E RanchalisDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Katherine M MunsonDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0001-8413-6498 Mitchell R VollgerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0002-8651-1615 Elsa BaltonDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Casie A GenettiThe Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4173-9947 Undiagnosed Diseases Network, Genomics Research to Elucidate the Genetics of Rare Diseases consortium, University of Washington Center for Rare Diseases Research
Monica H WojcikThe Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8162-5031 Alan H BeggsThe Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-8818-0568 Michael J BamshadDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Chia-Lin WeiDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0001-6820-0461 Katrina M DippleDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA.
Runjun D KumarDepartment of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA.
Elizabeth E BlueDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-0633-0305 Gail JarvikDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Jessica X ChongDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA.ORCID 0000-0002-1616-2448 Daniela M WittenDepartments of Statistics & Biostatistics, University of Washington, Seattle, WA, USA.ORCID 0000-0002-1764-1184 Anne O'Donnell-LuriaThe Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6418-9592 Andrew B StergachisDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.ORCID 0000-0002-1299-3674 Funding
University of Washington Mendelian Genomics Research Center (UW-MGRC)U01HG011744 · NHGRI · UNIVERSITY OF WASHINGTON · PI MICHAEL Joseph BAMSHAD, Evan Eichler · 2021 to 2026
$15.8MBroad Institute Mendelian Genomic Research CenterU01HG011755 · NHGRI · BROAD INSTITUTE, INC. · PI Anne O'Donnell-Luria, MICHAEL E TALKOWSKI · 2021 to 2026
$14.6MMedical Genetics Training GrantT32GM007454 · NIGMS · UNIVERSITY OF WASHINGTON · PI Gail Pairitz Jarvik, Andrew Ben Stergachis · 1985 to 2026
$6.9MPacific Northwest Undiagnosed Diseases Network Clinical SiteU01HG010233 · NHGRI · UNIVERSITY OF WASHINGTON · PI DIPPLE, KATRINA M, JARVIK, GAIL PAIRITZ · 2018 to 2022
$5.4MPacific Northwest Undiagnosed Diseases Network Clinical SiteU01NS134355 · NINDS · UNIVERSITY OF WASHINGTON · PI ELIZABETH ELOYCE BLUE, Katrina M Dipple · 2023 to 2026
$3.0MInvestigating the contribution of non-coding genetic variation to rare disordersDP5OD029630 · OD · UNIVERSITY OF WASHINGTON · PI STERGACHIS, ANDREW BEN · 2020 to 2024
$1.9MTooling for accurately studying the epigenome along the human pangenome referenceU01HG013744 · NHGRI · UNIVERSITY OF WASHINGTON · PI STERGACHIS, ANDREW BEN · 2024 to 2024
$1.4MThe regulatory landscape of segmentally duplicated genes: Implications for human evolution and diseaseK99GM155552 · NIGMS · UNIVERSITY OF WASHINGTON · PI VOLLGER, MITCHELL R. · 2024 to 2025
$160kNHGRI NIH HHS U01 HG010233NHGRI NIH HHS U01 HG011744NHGRI NIH HHS U01 HG011755NHGRI NIH HHS U01 HG013744NIGMS NIH HHS K99 GM155552NIGMS NIH HHS T32 GM007454NIH HHS DP5 OD029630NINDS NIH HHS U01 NS134355
6 · The paper itselfAbstract
Identifying pathogenic non-coding variants that contribute to Mendelian conditions remains challenging as the functional impact of these variants on gene function is often unknown. We present IsoRanker, a long-read transcriptome sequencing-based framework that prioritizes functionally relevant non-coding variants by detecting genes and novel isoforms with outlier expression, allelic imbalance, and/or nonsense-mediated decay (NMD). We generated paired cycloheximide-treated and untreated fibroblast transcriptomes from 31 individuals (3 individuals with known transcript-altering rare variants and 28 individuals with unsolved conditions) and linked transcripts to phased long-read genomes. IsoRanker successfully recovered known transcript alterations in this cohort and remained robust in subsampling analyses to cohorts of 11 individuals and ~5 million full-length transcripts per individual. However, performance was dependent upon
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PMID41292655
PMCPMC12642736
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