Dissecting splicing decisions and cell-to-cell variability with designed sequence libraries.
Alternative Splicing
Cloning, Molecular
Computational Biology
Gene Expression Profiling
Gene Library
High-Throughput Nucleotide Sequencing
Humans
K562 Cells
Machine Learning
Mutation
Protein Isoforms
/ genetics
Proteome
/ genetics
RNA Splice Sites
/ genetics
RNA, Messenger
/ genetics
Sequence Analysis, DNA
Single-Cell Analysis
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 10 2019
08 10 2019
Historique:
received:
27
11
2018
accepted:
22
09
2019
entrez:
10
10
2019
pubmed:
9
10
2019
medline:
20
2
2020
Statut:
epublish
Résumé
Most human genes are alternatively spliced, allowing for a large expansion of the proteome. The multitude of regulatory inputs to splicing limits the potential to infer general principles from investigating native sequences. Here, we create a rationally designed library of >32,000 splicing events to dissect the complexity of splicing regulation through systematic sequence alterations. Measuring RNA and protein splice isoforms allows us to investigate both cause and effect of splicing decisions, quantify diverse regulatory inputs and accurately predict (R
Identifiants
pubmed: 31594945
doi: 10.1038/s41467-019-12642-3
pii: 10.1038/s41467-019-12642-3
pmc: PMC6783452
doi:
Substances chimiques
Protein Isoforms
0
Proteome
0
RNA Splice Sites
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4572Références
Nature. 2010 Sep 9;467(7312):167-73
pubmed: 20829787
Genome Biol. 2018 Jun 1;19(1):71
pubmed: 29859120
Cell. 2014 Oct 23;159(3):487-98
pubmed: 25417102
Nucleic Acids Res. 2012 Apr;40(8):e57
pubmed: 22259036
Nat Genet. 2017 Jun;49(6):848-855
pubmed: 28416821
Genome Res. 2014 Mar;24(3):496-510
pubmed: 24299736
Genome Res. 2018 Jan;28(1):11-24
pubmed: 29242188
Semin Cell Dev Biol. 2014 Aug;32:11-21
pubmed: 24657192
Am J Hum Genet. 2008 Apr;82(4):834-48
pubmed: 18371932
Genome Res. 2019 Feb;29(2):171-183
pubmed: 30622120
Genome Res. 2011 Aug;21(8):1360-74
pubmed: 21659425
Trends Genet. 2015 May;31(5):274-80
pubmed: 25837375
Database (Oxford). 2016 Apr 07;2016:
pubmed: 27055826
Nature. 2013 Jun 13;498(7453):236-40
pubmed: 23685454
Mol Cell. 2018 Sep 20;71(6):1012-1026.e3
pubmed: 30174293
Curr Opin Genet Dev. 2007 Apr;17(2):107-12
pubmed: 17317149
Nature. 2010 May 6;465(7294):53-9
pubmed: 20445623
BMC Genomics. 2008 Jul 29;9:355
pubmed: 18664289
Algorithms Mol Biol. 2011 Nov 24;6:26
pubmed: 22115189
Wiley Interdiscip Rev RNA. 2015 May-Jun;6(3):311-26
pubmed: 25630614
Genome Biol. 2019 Mar 1;20(1):48
pubmed: 30823901
J Comput Biol. 2004;11(2-3):377-94
pubmed: 15285897
Nat Commun. 2017 May 08;8:15134
pubmed: 28480880
Nat Genet. 2002 May;31(1):69-73
pubmed: 11967532
Science. 2015 Jan 9;347(6218):1254806
pubmed: 25525159
Science. 2002 Aug 16;297(5584):1183-6
pubmed: 12183631
Cell Rep. 2012 May 31;1(5):543-56
pubmed: 22832277
Nat Commun. 2018 Feb 6;9(1):529
pubmed: 29410437
Mol Cancer Res. 2018 Mar;16(3):461-469
pubmed: 29330282
Mol Cell Biol. 2010 Apr;30(8):1878-86
pubmed: 20123971
Wiley Interdiscip Rev RNA. 2015 Jan-Feb;6(1):93-110
pubmed: 25155147
Mol Cell. 2011 Sep 16;43(6):1033-9
pubmed: 21925391
Cell. 2015 Oct 22;163(3):698-711
pubmed: 26496609
Curr Opin Genet Dev. 2011 Aug;21(4):373-9
pubmed: 21530232