SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads

Human Pangenome Reference Consortium

doi:10.1038/s41592-026-03045-6

SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads

Human Pangenome Reference Consortium

Research output: Contribution to journal › Article › peer-review

Abstract

Long-read RNA sequencing is a powerful technology to link transcript structures to genetic variants, but this type of analysis is not often performed owing to the lack of end-user tools. Here we introduce longcallR for joint single-nucleotide polymorphism calling, haplotype phasing and allele-specific analysis, which achieves high accuracy on benchmark datasets. Applied to 202 human samples, longcallR identified 88 significant allele-specific splicing events per sample on average, of which 46% involved unannotated junctions.

Original language	English (US)
Journal	Nature methods
DOIs	https://doi.org/10.1038/s41592-026-03045-6
State	Accepted/In press - 2026

All Science Journal Classification (ASJC) codes

Biotechnology
Biochemistry
Molecular Biology
Cell Biology

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10.1038/s41592-026-03045-6

Cite this

@article{f54c78bdbe0a479b86f5356376c93fbe,

title = "SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads",

abstract = "Long-read RNA sequencing is a powerful technology to link transcript structures to genetic variants, but this type of analysis is not often performed owing to the lack of end-user tools. Here we introduce longcallR for joint single-nucleotide polymorphism calling, haplotype phasing and allele-specific analysis, which achieves high accuracy on benchmark datasets. Applied to 202 human samples, longcallR identified 88 significant allele-specific splicing events per sample on average, of which 46\% involved unannotated junctions.",

author = "\{Human Pangenome Reference Consortium\} and Neng Huang and Heng Li and Giulia Zunino and Ivo Violich and Ying Zhou and Wenjin Zhang and Yoo, \{Dong Ahn\} and Kai Ye and Zheng Xu and Zilan Xin and Whelan, \{Conor V.\} and Wenger, \{Aaron M.\} and Ting Wang and Wang, \{Lisa E.\} and Charles Wang and Walenz, \{Brian P.\} and Vollger, \{Mitchell R.\} and Flavia Villani and Rahul Varki and Ungaro, \{Matteo Tommaso\} and Mohammed Uddin and Tricomi, \{Francesca Floriana\} and Chad Tomlinson and Tierney, \{Jack A.S.\} and Arda S{\"o}ylev and Yoshihiko Suzuki and Suner, \{Marie Marthe\} and Stergachis, \{Andrew B.\} and Nicole Soranzo and Marco Sollitto and Solar, \{Steven J.\} and Linn{\'e}a Smeds and Jouni Sir{\'e}n and Swati Sinha and Shivakumar, \{Vikram S.\} and Ruhollah Shemirani and Shadi Shahatit and Kishwar Shafin and Mahsa Shabani and Seligmann, \{William E.\} and Aarushi Sehgal and Scheinfeldt, \{Laura B.\} and Schatz, \{Michael C.\} and Samuel Sacco and Farnaz Salehi and Arang Rhie and Luyao Ren and Alessandro Raveane and Mikko Rautiainen and Makova, \{Kateryna D.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2026.",

year = "2026",

doi = "10.1038/s41592-026-03045-6",

language = "English (US)",

journal = "Nature methods",

issn = "1548-7091",

publisher = "Nature Research",

}

TY - JOUR

T1 - SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads

AU - Human Pangenome Reference Consortium

AU - Huang, Neng

AU - Li, Heng

AU - Zunino, Giulia

AU - Violich, Ivo

AU - Zhou, Ying

AU - Zhang, Wenjin

AU - Yoo, Dong Ahn

AU - Ye, Kai

AU - Xu, Zheng

AU - Xin, Zilan

AU - Whelan, Conor V.

AU - Wenger, Aaron M.

AU - Wang, Ting

AU - Wang, Lisa E.

AU - Wang, Charles

AU - Walenz, Brian P.

AU - Vollger, Mitchell R.

AU - Villani, Flavia

AU - Varki, Rahul

AU - Ungaro, Matteo Tommaso

AU - Uddin, Mohammed

AU - Tricomi, Francesca Floriana

AU - Tomlinson, Chad

AU - Tierney, Jack A.S.

AU - Söylev, Arda

AU - Suzuki, Yoshihiko

AU - Suner, Marie Marthe

AU - Stergachis, Andrew B.

AU - Soranzo, Nicole

AU - Sollitto, Marco

AU - Solar, Steven J.

AU - Smeds, Linnéa

AU - Sirén, Jouni

AU - Sinha, Swati

AU - Shivakumar, Vikram S.

AU - Shemirani, Ruhollah

AU - Shahatit, Shadi

AU - Shafin, Kishwar

AU - Shabani, Mahsa

AU - Seligmann, William E.

AU - Sehgal, Aarushi

AU - Scheinfeldt, Laura B.

AU - Schatz, Michael C.

AU - Sacco, Samuel

AU - Salehi, Farnaz

AU - Rhie, Arang

AU - Ren, Luyao

AU - Raveane, Alessandro

AU - Rautiainen, Mikko

AU - Makova, Kateryna D.

PY - 2026

Y1 - 2026

N2 - Long-read RNA sequencing is a powerful technology to link transcript structures to genetic variants, but this type of analysis is not often performed owing to the lack of end-user tools. Here we introduce longcallR for joint single-nucleotide polymorphism calling, haplotype phasing and allele-specific analysis, which achieves high accuracy on benchmark datasets. Applied to 202 human samples, longcallR identified 88 significant allele-specific splicing events per sample on average, of which 46% involved unannotated junctions.

AB - Long-read RNA sequencing is a powerful technology to link transcript structures to genetic variants, but this type of analysis is not often performed owing to the lack of end-user tools. Here we introduce longcallR for joint single-nucleotide polymorphism calling, haplotype phasing and allele-specific analysis, which achieves high accuracy on benchmark datasets. Applied to 202 human samples, longcallR identified 88 significant allele-specific splicing events per sample on average, of which 46% involved unannotated junctions.

UR - https://www.scopus.com/pages/publications/105035303695

UR - https://www.scopus.com/pages/publications/105035303695#tab=citedBy

U2 - 10.1038/s41592-026-03045-6

DO - 10.1038/s41592-026-03045-6

M3 - Article

C2 - 41912802

AN - SCOPUS:105035303695

SN - 1548-7091

JO - Nature methods

JF - Nature methods

ER -

SNP calling, haplotype phasing and allele-specific analysis with long RNA-seq reads

Abstract

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