A sequence-based, deep learning model accurately predicts RNA splicing branchpoints

RNA
Joseph M Paggi, Gill Bejerano

Abstract

Experimental detection of RNA splicing branchpoints is difficult. To date, high-confidence experimental annotations exist for 18% of 3' splice sites in the human genome. We develop a deep-learning-based branchpoint predictor, LaBranchoR, which predicts a correct branchpoint for at least 75% of 3' splice sites genome-wide. Detailed analysis of cases in which our predicted branchpoint deviates from experimental data suggests a correct branchpoint is predicted in over 90% of cases. We use our predicted branchpoints to identify a novel sequence element upstream of branchpoints consistent with extended U2 snRNA base-pairing, show an association between weak branchpoints and alternative splicing, and explore the effects of genetic variants on branchpoints. We provide genome-wide branchpoint annotations and in silico mutagenesis scores at http://bejerano.stanford.edu/labranchor.

References

Oct 23, 1997·Neural Computation·S Hochreiter, J Schmidhuber
Aug 3, 2004·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Gene Yeo, Christopher B Burge
Jul 19, 2005·Genome Research·Adam SiepelDavid Haussler
Oct 28, 2009·Genome Research·Katherine S PollardAdam Siepel
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Nov 9, 2010·Nature Methods·Yarden KatzChristopher B Burge
Dec 3, 2010·PLoS Computational Biology·André CorveloEduardo Eyras
Jun 21, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kian Huat LimWilliam G Fairbrother
Jul 29, 2011·Nucleic Acids Research·Peter J ShepardKlemens J Hertel
Sep 1, 2011·Molecular Biology and Evolution·Ashley FarlowChristian Schlötterer
Oct 7, 2011·Protein & Cell·Andrew T YuYi-Tao Yu
Apr 7, 2012·Trends in Biochemical Sciences·Aaron A Hoskins, Melissa J Moore
Jun 19, 2012·Nature Structural & Molecular Biology·Allison J TaggartWilliam G Fairbrother
Dec 27, 2013·Nucleic Acids Research·Elzbieta KierzekRyszard Kierzek
Nov 20, 2015·Nucleic Acids Research·Melissa J LandrumDonna R Maglott
Jul 28, 2016·Nature·Wojciech P GalejKiyoshi Nagai
Aug 19, 2016·Nature·Monkol LekUNKNOWN Exome Aggregation Consortium
Jan 12, 2017·Nature·Karl BertramReinhard Lührmann
Nov 2, 2017·Bioinformatics·Bethany SignalTim R Mercer

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Citations

Feb 26, 2019·Nature Genetics·Karthik A JagadeeshGill Bejerano
Apr 27, 2019·ELife·Leonhard WachutkaPatrick Cramer
Oct 2, 2019·Nature Structural & Molecular Biology·Michael BrieseJernej Ule
Dec 1, 2019·Genome Biology·Sébastien LemaireDidier Auboeuf
Jun 9, 2021·Nature Communications·Dadi GaoSusan A Slaugenhaupt
Jun 29, 2021·Frontiers in Molecular Biosciences·Jan ZrimecAleksej Zelezniak
Aug 4, 2021·Nature Reviews. Genetics·Aaron K WongOlga G Troyanskaya

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