A correlation with exon expression approach to identify cis-regulatory elements for tissue-specific alternative splicing

Das, Debopriya; Clark, Tyson A.; Schweitzer, Anthony; Yamamoto, Miki; Marr, Henry; Arribere, Josh; Minovitsky, Simon; Poliakov, Alexander; Dubchak, Inna; Blume, John E.; Conboy, John G.

doi:10.1093/nar/gkm485

A correlation with exon expression approach to identify cis-regulatory elements for tissue-specific alternative splicing

Journal Article · Tue Jul 10 00:00:00 EDT 2007 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkm485· OSTI ID:1625425

Das, Debopriya ^[1]; Clark, Tyson A. ^[2]; Schweitzer, Anthony ^[2]; Yamamoto, Miki ^[3]; Marr, Henry ^[3]; Arribere, Josh ^[3]; Minovitsky, Simon ^[4]; Poliakov, Alexander ^[5]; Dubchak, Inna ^[5]; Blume, John E. ^[2]; Conboy, John G. ^[3]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division; DOE/OSTI
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Genomics Division
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
Affymetrix, Inc., Santa Clara, CA (United States)
Affymetrix, Inc., Santa Clara, CA (United States)

Correlation of motif occurrences with gene expression intensity is an effective strategy for elucidating transcriptional cis-regulatory logic. Here we demonstrate that this approach can also identify cis-regulatory elements for alternative pre-mRNA splicing. Using data from a human exon microarray, we identified 56 cassette exons that exhibited higher transcript-normalized expression in muscle than in other normal adult tissues. Intron sequences flanking these exons were then analyzed to identify candidate regulatory motifs for muscle-specific alternative splicing. Correlation of motif parameters with gene-normalized exon expression levels was examined using linear regression and linear splines on RNA words and degenerate weight matrices, respectively. Our unbiased analysis uncovered multiple candidate regulatory motifs for muscle-specific splicing, many of which are phylogenetically conserved among vertebrate genomes. The most prominent downstream motifs were binding sites for Fox1- and CELF-related splicing factors, and a branchpoint-like element ACUAAC; pyrimidine-rich elements resembling PTB-binding sites were most significant in upstream introns. Intriguingly, our systematic study indicates a paucity of novel muscle-specific elements that are dominant in short proximal intronic regions. We propose that Fox and CELF proteins play major roles in enforcing the muscle-specific alternative splicing program, facilitating expression of unique isoforms of cytoskeletal proteins critical to muscle cell function.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC); Univ. of California, Berkeley, CA (United States)

Sponsoring Organization:: National Aeronautics and Space Administration (NASA); National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC02-05CH11231; AC03-76SF00098

OSTI ID:: 1625425

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 14 Vol. 35; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

References (75)

Towards a Splicing Code Fu, Xiang-Dong Cell, Vol. 119, Issue 6 https://doi.org/10.1016/j.cell.2004.11.039	journal	December 2004
Alternative Splicing: New Insights from Global Analyses Blencowe, Benjamin J. Cell, Vol. 126, Issue 1 https://doi.org/10.1016/j.cell.2006.06.023	journal	July 2006
Polypyrimidine Tract Binding Protein Blocks the 5′ Splice Site-Dependent Assembly of U2AF and the Prespliceosomal E Complex Sharma, Shalini; Falick, Arnold M.; Black, Douglas L. Molecular Cell, Vol. 19, Issue 4 https://doi.org/10.1016/j.molcel.2005.07.014	journal	August 2005
Novel modes of splicing repression by PTB Spellman, Rachel; Smith, Christopher W. J. Trends in Biochemical Sciences, Vol. 31, Issue 2 https://doi.org/10.1016/j.tibs.2005.12.003	journal	February 2006
Conditional knockout mice to study alternative splicing in vivo Xu, Xiangdong; Fu, Xiang-Dong Methods, Vol. 37, Issue 4 https://doi.org/10.1016/j.ymeth.2005.07.019	journal	December 2005
Detection and measurement of alternative splicing using splicing-sensitive microarrays Srinivasan, Karpagam; Shiue, Lily; Hayes, Justin D. Methods, Vol. 37, Issue 4 https://doi.org/10.1016/j.ymeth.2005.09.007	journal	December 2005
Neuron-specific Alternative Splicing of Nonmuscle Myosin II Heavy Chain-B Pre-mRNA Requires a Cis-acting Intron Sequence Kawamoto, Sachiyo Journal of Biological Chemistry, Vol. 271, Issue 30 https://doi.org/10.1016/s0021-9258(19)86956-9	journal	July 1996
Loss of the Muscle-Specific Chloride Channel in Type 1 Myotonic Dystrophy Due to Misregulated Alternative Splicing Charlet-B., Nicolas; Savkur, Rajesh S.; Singh, Gopal Molecular Cell, Vol. 10, Issue 1 https://doi.org/10.1016/s1097-2765(02)00572-5	journal	July 2002
Region-specific alternative splicing in the nervous system: Implications for regulation by the RNA-binding protein NAPOR Zhang, Wenqing; Liu, Haiying; Han, Kyoungha RNA, Vol. 8, Issue 5 https://doi.org/10.1017/s1355838202027036	journal	May 2002
Initial sequencing and analysis of the human genome Lander, Eric S.; Linton, Lauren M. Nature, Vol. 409, Issue 6822, p. 860-921 https://doi.org/10.1038/35057062	journal	February 2001
Regulatory element detection using correlation with expression Bussemaker, Harmen J.; Li, Hao; Siggia, Eric D. Nature Genetics, Vol. 27, Issue 2 https://doi.org/10.1038/84792	journal	February 2001
Assessing computational tools for the discovery of transcription factor binding sites Tompa, Martin; Li, Nan; Bailey, Timothy L. Nature Biotechnology, Vol. 23, Issue 1 https://doi.org/10.1038/nbt1053	journal	January 2005
Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy Savkur, Rajesh S.; Philips, Anne V.; Cooper, Thomas A. Nature Genetics, Vol. 29, Issue 1 https://doi.org/10.1038/ng704	journal	August 2001
Intronic CA-repeat and CA-rich elements: a new class of regulators of mammalian alternative splicing Hui, Jingyi; Hung, Lee-Hsueh; Heiner, Monika The EMBO Journal, Vol. 24, Issue 11 https://doi.org/10.1038/sj.emboj.7600677	journal	May 2005
Variation in sequence and organization of splicing regulatory elements in vertebrate genes Yeo, G.; Hoon, S.; Venkatesh, B. Proceedings of the National Academy of Sciences, Vol. 101, Issue 44 https://doi.org/10.1073/pnas.0404901101	journal	October 2004
Identifying tissue-selective transcription factor binding sites in vertebrate promoters Smith, A. D.; Sumazin, P.; Zhang, M. Q. Proceedings of the National Academy of Sciences, Vol. 102, Issue 5 https://doi.org/10.1073/pnas.0406123102	journal	January 2005
Interacting models of cooperative gene regulation Das, D.; Banerjee, N.; Zhang, M. Q. Proceedings of the National Academy of Sciences, Vol. 101, Issue 46 https://doi.org/10.1073/pnas.0407365101	journal	November 2004
Integrating regulatory motif discovery and genome-wide expression analysis Conlon, E. M.; Liu, X. S.; Lieb, J. D. Proceedings of the National Academy of Sciences, Vol. 100, Issue 6 https://doi.org/10.1073/pnas.0630591100	journal	March 2003
Statistical significance for genomewide studies Storey, J. D.; Tibshirani, R. Proceedings of the National Academy of Sciences, Vol. 100, Issue 16, p. 9440-9445 https://doi.org/10.1073/pnas.1530509100	journal	July 2003
A systematic approach to reconstructing transcription networks in Saccharomyces cerevisiae Wang, W.; Cherry, J. M.; Botstein, D. Proceedings of the National Academy of Sciences, Vol. 99, Issue 26 https://doi.org/10.1073/pnas.252638199	journal	December 2002
Characterization of the Intronic Splicing Silencers Flanking FGFR2 Exon IIIb Wagner, Eric J.; Baraniak, Andrew P.; Sessions, October M. Journal of Biological Chemistry, Vol. 280, Issue 14 https://doi.org/10.1074/jbc.m414492200	journal	April 2005
DNA binding sites: representation and discovery Stormo, G. D. Bioinformatics, Vol. 16, Issue 1 https://doi.org/10.1093/bioinformatics/16.1.16	journal	January 2000
Modeling within-motif dependence for transcription factor binding site predictions Zhou, Q.; Liu, J. S. Bioinformatics, Vol. 20, Issue 6 https://doi.org/10.1093/bioinformatics/bth006	journal	January 2004
Mining ChIP-chip data for transcription factor and cofactor binding sites Smith, A. D.; Sumazin, P.; Das, D. Bioinformatics, Vol. 21, Issue Suppl 1 https://doi.org/10.1093/bioinformatics/bti1043	journal	June 2005
A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG Jin, Y. The EMBO Journal, Vol. 22, Issue 4 https://doi.org/10.1093/emboj/cdg089	journal	February 2003
Low conservation of alternative splicing patterns in the human and mouse genomes Nurtdinov, R. N. Human Molecular Genetics, Vol. 12, Issue 11 https://doi.org/10.1093/hmg/ddg137	journal	June 2003
MATCHTM: a tool for searching transcription factor binding sites in DNA sequences Kel, A. E. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg585	journal	July 2003
ESEfinder: a web resource to identify exonic splicing enhancers Cartegni, L. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg616	journal	July 2003
The splicing regulatory element, UGCAUG, is phylogenetically and spatially conserved in introns that flank tissue-specific alternative exons Minovitsky, S. Nucleic Acids Research, Vol. 33, Issue 2 https://doi.org/10.1093/nar/gki210	journal	January 2005
Tissue-dependent isoforms of mammalian Fox-1 homologs are associated with tissue-specific splicing activities Nakahata, S. Nucleic Acids Research, Vol. 33, Issue 7 https://doi.org/10.1093/nar/gki338	journal	April 2005
Intronic Sequences Flanking Alternatively Spliced Exons Are Conserved Between Human and Mouse Sorek, R. Genome Research, Vol. 13, Issue 7 https://doi.org/10.1101/gr.1208803	journal	July 2003
BLAT---The BLAST-Like Alignment Tool Kent, W. J. Genome Research, Vol. 12, Issue 4 https://doi.org/10.1101/gr.229202	journal	March 2002
LAGAN and Multi-LAGAN: Efficient Tools for Large-Scale Multiple Alignment of Genomic DNA Brudno, M. Genome Research, Vol. 13, Issue 4 https://doi.org/10.1101/gr.926603	journal	March 2003
Genomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays Clark, T. A. Science, Vol. 296, Issue 5569 https://doi.org/10.1126/science.1069415	journal	May 2002
Predictive Identification of Exonic Splicing Enhancers in Human Genes Fairbrother, W. G. Science, Vol. 297, Issue 5583 https://doi.org/10.1126/science.1073774	journal	July 2002
Genome-Wide Survey of Human Alternative Pre-mRNA Splicing with Exon Junction Microarrays Johnson, J. M. Science, Vol. 302, Issue 5653 https://doi.org/10.1126/science.1090100	journal	December 2003
Role for Fox-1/Fox-2 in Mediating the Neuronal Pathway of Calcitonin/Calcitonin Gene-Related Peptide Alternative RNA Processing Zhou, H. -L.; Baraniak, A. P.; Lou, H. Molecular and Cellular Biology, Vol. 27, Issue 3 https://doi.org/10.1128/mcb.01015-06	journal	November 2006
Muscle-Specific Splicing of a Heterologous Exon Mediated by a Single Muscle-Specific Splicing Enhancer from the Cardiac Troponin T Gene Cooper, Thomas A. Molecular and Cellular Biology, Vol. 18, Issue 8 https://doi.org/10.1128/mcb.18.8.4519	journal	August 1998
Polypyrimidine Tract Binding Protein Antagonizes Exon Definition Wagner, Eric J.; Garcia-Blanco, Mariano A. Molecular and Cellular Biology, Vol. 21, Issue 10 https://doi.org/10.1128/mcb.21.10.3281-3288.2001	journal	May 2001
The CELF Family of RNA Binding Proteins Is Implicated in Cell-Specific and Developmentally Regulated Alternative Splicing Ladd, Andrea N.; Charlet-B., Nicolas; Cooper, Thomas A. Molecular and Cellular Biology, Vol. 21, Issue 4 https://doi.org/10.1128/mcb.21.4.1285-1296.2001	journal	February 2001
Exon Inclusion Is Dependent on Predictable Exonic Splicing Enhancers Zhang, Xiang H. -F.; Kangsamaksin, Thaned; Chao, Mann S. P. Molecular and Cellular Biology, Vol. 25, Issue 16 https://doi.org/10.1128/mcb.25.16.7323-7332.2005	journal	August 2005
Homologues of the Caenorhabditis elegans Fox-1 Protein Are Neuronal Splicing Regulators in Mammals Underwood, Jason G.; Boutz, Paul L.; Dougherty, Joseph D. Molecular and Cellular Biology, Vol. 25, Issue 22 https://doi.org/10.1128/mcb.25.22.10005-10016.2005	journal	November 2005
Fox-2 Mediates Epithelial Cell-Specific Fibroblast Growth Factor Receptor 2 Exon Choice Baraniak, A. P.; Chen, J. R.; Garcia-Blanco, M. A. Molecular and Cellular Biology, Vol. 26, Issue 4 https://doi.org/10.1128/mcb.26.4.1209-1222.2006	journal	January 2006
Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array Gardina, Paul J.; Clark, Tyson A.; Shimada, Brian BMC Genomics, Vol. 7, Issue 1 https://doi.org/10.1186/1471-2164-7-325	journal	December 2006
GoMiner: a resource for biological interpretation of genomic and proteomic data Zeeberg, Barry R.; Feng, Weimin; Wang, Geoffrey Genome Biology, Vol. 4, Issue 4 https://doi.org/10.1186/gb-2003-4-4-r28	journal	April 2003
Discovery of tissue-specific exons using comprehensive human exon microarrays Clark, Tyson A.; Schweitzer, Anthony C.; Chen, Tina X. Genome Biology, Vol. 8, Issue 4 https://doi.org/10.1186/gb-2007-8-4-r64	journal	January 2007
Exon repression by polypyrimidine tract binding protein Amir-Ahmady, B. RNA, Vol. 11, Issue 5 https://doi.org/10.1261/rna.2250405	journal	May 2005
The Elements of Statistical Learning Hastie, Trevor; Friedman, Jerome; Tibshirani, Robert Springer Series in Statistics https://doi.org/10.1007/978-0-387-21606-5	book	January 2001
Selection of DNA binding sites by regulatory proteins Berg, Otto G.; von Hippel, Peter H. Journal of Molecular Biology, Vol. 193, Issue 4 https://doi.org/10.1016/0022-2836(87)90354-8	journal	February 1987
Neuron-specific Alternative Splicing of Nonmuscle Myosin II Heavy Chain-B Pre-mRNA Requires a Cis-acting Intron Sequence Kawamoto, Sachiyo Journal of Biological Chemistry, Vol. 271, Issue 30 https://doi.org/10.1016/S0021-9258(19)86956-9	journal	July 1996
Loss of the Muscle-Specific Chloride Channel in Type 1 Myotonic Dystrophy Due to Misregulated Alternative Splicing Charlet-B., Nicolas; Savkur, Rajesh S.; Singh, Gopal Molecular Cell, Vol. 10, Issue 1 https://doi.org/10.1016/S1097-2765(02)00572-5	journal	July 2002
Systematic Identification and Analysis of Exonic Splicing Silencers Wang, Zefeng; Rolish, Michael E.; Yeo, Gene Cell, Vol. 119, Issue 6 https://doi.org/10.1016/j.cell.2004.11.010	journal	December 2004
Region-specific alternative splicing in the nervous system: Implications for regulation by the RNA-binding protein NAPOR Zhang, Wenqing; Liu, Haiying; Han, Kyoungha RNA, Vol. 8, Issue 5 https://doi.org/10.1017/S1355838202027036	journal	May 2002
Adaptively inferring human transcriptional subnetworks Das, Debopriya; Nahlé, Zaher; Zhang, Michael Q Molecular Systems Biology, Vol. 2, Issue 1, Article No. 0029 https://doi.org/10.1038/msb4100067	journal	June 2006
Nova regulates brain-specific splicing to shape the synapse Ule, Jernej; Ule, Aljaž; Spencer, Joanna Nature Genetics, Vol. 37, Issue 8 https://doi.org/10.1038/ng1610	journal	July 2005
Genome-wide analysis of mouse transcripts using exon microarrays and factor graphs Frey, Brendan J.; Mohammad, Naveed; Morris, Quaid D. Nature Genetics, Vol. 37, Issue 9 https://doi.org/10.1038/ng1630	journal	August 2005
Characterization of the Intronic Splicing Silencers Flanking FGFR2 Exon IIIb Wagner, Eric J.; Baraniak, Andrew P.; Sessions, October M. Journal of Biological Chemistry, Vol. 280, Issue 14 https://doi.org/10.1074/jbc.M414492200	journal	April 2005
Fox-2 Splicing Factor Binds to a Conserved Intron Motif to Promote Inclusion of Protein 4.1R Alternative Exon 16 Ponthier, Julie L.; Schluepen, Christina; Chen, Weiguo Journal of Biological Chemistry, Vol. 281, Issue 18 https://doi.org/10.1074/jbc.M511556200	journal	March 2006
Identification of regulatory elements using a feature selection method Keles, S.; van der Laan, M.; Eisen, M. B. Bioinformatics, Vol. 18, Issue 9 https://doi.org/10.1093/bioinformatics/18.9.1167	journal	September 2002
Similarity of position frequency matrices for transcription factor binding sites Schones, D. E.; Sumazin, P.; Zhang, M. Q. Bioinformatics, Vol. 21, Issue 3 https://doi.org/10.1093/bioinformatics/bth480	journal	August 2004
A sequence compilation and comparison of exons that are alternatively spliced in neurons Stamm, Stefan; Zhang, Mike Q.; Marr, Thomas G. Nucleic Acids Research, Vol. 22, Issue 9 https://doi.org/10.1093/nar/22.9.1515	journal	January 1994
Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing Brudno, M. Nucleic Acids Research, Vol. 29, Issue 11 https://doi.org/10.1093/nar/29.11.2338	journal	June 2001
Conserved sequence elements associated with exon skipping Miriami, E. Nucleic Acids Research, Vol. 31, Issue 7 https://doi.org/10.1093/nar/gkg279	journal	April 2003
Sequence Information for the Splicing of Human Pre-mRNA Identified by Support Vector Machine Classification Zhang, X. H-F. Genome Research, Vol. 13, Issue 12 https://doi.org/10.1101/gr.1679003	journal	December 2003
The Sequence of the Human Genome Venter, J. Craig; Adams, Mark D.; Myers, Eugene W. Science, Vol. 291, Issue 5507 https://doi.org/10.1126/science.1058040	journal	February 2001
Role for Fox-1/Fox-2 in Mediating the Neuronal Pathway of Calcitonin/Calcitonin Gene-Related Peptide Alternative RNA Processing Zhou, H. -L.; Baraniak, A. P.; Lou, H. Molecular and Cellular Biology, Vol. 27, Issue 3 https://doi.org/10.1128/MCB.01015-06	journal	November 2006
Muscle-Specific Splicing of a Heterologous Exon Mediated by a Single Muscle-Specific Splicing Enhancer from the Cardiac Troponin T Gene Cooper, Thomas A. Molecular and Cellular Biology, Vol. 18, Issue 8 https://doi.org/10.1128/MCB.18.8.4519	journal	August 1998
Polypyrimidine Tract Binding Protein Antagonizes Exon Definition Wagner, Eric J.; Garcia-Blanco, Mariano A. Molecular and Cellular Biology, Vol. 21, Issue 10 https://doi.org/10.1128/MCB.21.10.3281-3288.2001	journal	May 2001
The CELF Family of RNA Binding Proteins Is Implicated in Cell-Specific and Developmentally Regulated Alternative Splicing Ladd, Andrea N.; Charlet-B., Nicolas; Cooper, Thomas A. Molecular and Cellular Biology, Vol. 21, Issue 4 https://doi.org/10.1128/MCB.21.4.1285-1296.2001	journal	February 2001
Exon Inclusion Is Dependent on Predictable Exonic Splicing Enhancers Zhang, Xiang H. -F.; Kangsamaksin, Thaned; Chao, Mann S. P. Molecular and Cellular Biology, Vol. 25, Issue 16 https://doi.org/10.1128/MCB.25.16.7323-7332.2005	journal	August 2005
Homologues of the Caenorhabditis elegans Fox-1 Protein Are Neuronal Splicing Regulators in Mammals Underwood, Jason G.; Boutz, Paul L.; Dougherty, Joseph D. Molecular and Cellular Biology, Vol. 25, Issue 22 https://doi.org/10.1128/MCB.25.22.10005-10016.2005	journal	November 2005
Fox-2 Mediates Epithelial Cell-Specific Fibroblast Growth Factor Receptor 2 Exon Choice Baraniak, A. P.; Chen, J. R.; Garcia-Blanco, M. A. Molecular and Cellular Biology, Vol. 26, Issue 4 https://doi.org/10.1128/MCB.26.4.1209-1222.2006	journal	January 2006
Mechanisms of Alternative Pre-Messenger RNA Splicing Black, Douglas L. Annual Review of Biochemistry, Vol. 72, Issue 1 https://doi.org/10.1146/annurev.biochem.72.121801.161720	journal	June 2003
Unusual Intron Conservation near Tissue-Regulated Exons Found by Splicing Microarrays Sugnet, Charles W.; Srinivasan, Karpagam; Clark, Tyson A. PLoS Computational Biology, Vol. 2, Issue 1 https://doi.org/10.1371/journal.pcbi.0020004	journal	January 2006
Intronic Alternative Splicing Regulators Identified by Comparative Genomics in Nematodes Kabat, Jennifer L.; Barberan-Soler, Sergio; McKenna, Paul PLoS Computational Biology, Vol. 2, Issue 7 https://doi.org/10.1371/journal.pcbi.0020086	journal	July 2006

Cited By (31)

Fox-1 family of RNA-binding proteins Kuroyanagi, Hidehito Cellular and Molecular Life Sciences, Vol. 66, Issue 24 https://doi.org/10.1007/s00018-009-0120-5	journal	August 2009
Neuronal Elav-like (Hu) Proteins Regulate RNA Splicing and Abundance to Control Glutamate Levels and Neuronal Excitability Ince-Dunn, Gulayse; Okano, Hirotaka J.; Jensen, Kirk B. Neuron, Vol. 75, Issue 6 https://doi.org/10.1016/j.neuron.2012.07.009	journal	September 2012
Rbfox-regulated alternative splicing is critical for zebrafish cardiac and skeletal muscle functions Gallagher, Thomas L.; Arribere, Joshua A.; Geurts, Paul A. Developmental Biology, Vol. 359, Issue 2 https://doi.org/10.1016/j.ydbio.2011.08.025	journal	November 2011
Splicing by cell type Arias, Mauricio A.; Ke, Shengdong; Chasin, Lawrence A. Nature Biotechnology, Vol. 28, Issue 7 https://doi.org/10.1038/nbt0710-686	journal	July 2010
Expression of 24,426 human alternative splicing events and predicted cis regulation in 48 tissues and cell lines Castle, John C.; Zhang, Chaolin; Shah, Jyoti K. Nature Genetics, Vol. 40, Issue 12 https://doi.org/10.1038/ng.264	journal	November 2008
FIRMA: a method for detection of alternative splicing from exon array data Purdom, E.; Simpson, K. M.; Robinson, M. D. Bioinformatics, Vol. 24, Issue 15 https://doi.org/10.1093/bioinformatics/btn284	journal	June 2008
Model-based detection of alternative splicing signals Barash, Yoseph; Blencowe, Benjamin J.; Frey, Brendan J. Bioinformatics, Vol. 26, Issue 12 https://doi.org/10.1093/bioinformatics/btq200	journal	June 2010
Conserved elements associated with ribosomal genes and their trans-splice acceptor sites in Caenorhabditis elegans Sleumer, Monica C.; Mah, Allan K.; Baillie, David L. Nucleic Acids Research, Vol. 38, Issue 9 https://doi.org/10.1093/nar/gkq003	journal	January 2010
Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments Richard, Hugues; Schulz, Marcel H.; Sultan, Marc Nucleic Acids Research, Vol. 38, Issue 10 https://doi.org/10.1093/nar/gkq041	journal	February 2010
Global regulation of alternative splicing during myogenic differentiation Bland, Christopher S.; Wang, Eric T.; Vu, Anthony Nucleic Acids Research, Vol. 38, Issue 21 https://doi.org/10.1093/nar/gkq614	journal	July 2010
ARH-seq: identification of differential splicing in RNA-seq data Rasche, Axel; Lienhard, Matthias; Yaspo, Marie-Laure Nucleic Acids Research, Vol. 42, Issue 14 https://doi.org/10.1093/nar/gku495	journal	June 2014
Identifying differential exon splicing using linear models and correlation coefficients Shah, Sonia H.; Pallas, Jacqueline A. BMC Bioinformatics, Vol. 10, Issue 1 https://doi.org/10.1186/1471-2105-10-26	journal	January 2009
Genome-wide prediction of cis-acting RNA elements regulating tissue-specific pre-mRNA alternative splicing Wang, Xin; Wang, Kejun; Radovich, Milan BMC Genomics, Vol. 10, Issue S1 https://doi.org/10.1186/1471-2164-10-s1-s4	journal	July 2009
Identification of conserved splicing motifs in mutually exclusive exons of 15 insect species Buendia, Patricia; Tyree, John; Loredo, Robert BMC Genomics, Vol. 13, Issue Suppl 2 https://doi.org/10.1186/1471-2164-13-s2-s1	journal	January 2012
Prediction of alternatively skipped exons and splicing enhancers from exon junction arrays Kechris, Katerina; Yang, Yee; Yeh, Ru-Fang BMC Genomics, Vol. 9, Issue 1 https://doi.org/10.1186/1471-2164-9-551	journal	January 2008
Studying alternative splicing regulatory networks through partial correlation analysis Chen, Liang; Zheng, Sika Genome Biology, Vol. 10, Issue 1 https://doi.org/10.1186/gb-2009-10-1-r3	journal	January 2009
A computational approach for genome-wide mapping of splicing factor binding sites Akerman, Martin; David-Eden, Hilda; Pinter, Ron Y. Genome Biology, Vol. 10, Issue 3 https://doi.org/10.1186/gb-2009-10-3-r30	journal	January 2009
Intronic motif pairs cooperate across exons to promote pre-mRNA splicing Ke, Shengdong; Chasin, Lawrence A. Genome Biology, Vol. 11, Issue 8 https://doi.org/10.1186/gb-2010-11-8-r84	journal	January 2010
Diversification of the muscle proteome through alternative splicing Nakka, Kiran; Ghigna, Claudia; Gabellini, Davide Skeletal Muscle, Vol. 8, Issue 1 https://doi.org/10.1186/s13395-018-0152-3	journal	March 2018
A Primer on Regression Methods for Decoding cis-Regulatory Logic Das, Debopriya; Pellegrini, Matteo; Gray, Joe W. PLoS Computational Biology, Vol. 5, Issue 1 https://doi.org/10.1371/journal.pcbi.1000269	journal	January 2009
A Global View of Cancer-Specific Transcript Variants by Subtractive Transcriptome-Wide Analysis He, Chunjiang; Zhou, Fang; Zuo, Zhixiang PLoS ONE, Vol. 4, Issue 3 https://doi.org/10.1371/journal.pone.0004732	journal	March 2009
Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules Park, Ji Yeon; Li, Wencheng; Zheng, Dinghai PLoS ONE, Vol. 6, Issue 7 https://doi.org/10.1371/journal.pone.0022391	journal	July 2011
A Biophysical Model for Identifying Splicing Regulatory Elements and Their Interactions Wen, Ji; Chen, Zhibin; Cai, Xiaodong PLoS ONE, Vol. 8, Issue 1 https://doi.org/10.1371/journal.pone.0054885	journal	January 2013
Neural Differentiation Modulates the Vertebrate Brain Specific Splicing Program Madgwick, Alicia; Fort, Philippe; Hanson, Peter S. PLOS ONE, Vol. 10, Issue 5 https://doi.org/10.1371/journal.pone.0125998	journal	May 2015
Identification of Targets of CUG-BP, Elav-Like Family Member 1 (CELF1) Regulation in Embryonic Heart Muscle Blech-Hermoni, Yotam; Dasgupta, Twishasri; Coram, Ryan J. PLOS ONE, Vol. 11, Issue 2 https://doi.org/10.1371/journal.pone.0149061	journal	February 2016
Deciphering the splicing code Barash, Yoseph; Calarco, John A.; Gao, Weijun Nature, Vol. 465, Issue 7294 https://doi.org/10.1038/nature09000	journal	May 2010
RNA processing and its regulation: global insights into biological networks Licatalosi, Donny D.; Darnell, Robert B. Nature Reviews Genetics, Vol. 11, Issue 1 https://doi.org/10.1038/nrg2673	journal	January 2010
Cancer-associated regulation of alternative splicing Venables, Julian P.; Klinck, Roscoe; Koh, ChuShin Nature Structural & Molecular Biology, Vol. 16, Issue 6 https://doi.org/10.1038/nsmb.1608	journal	May 2009
A postnatal switch of CELF and MBNL proteins reprograms alternative splicing in the developing heart Kalsotra, A.; Xiao, X.; Ward, A. J. Proceedings of the National Academy of Sciences, Vol. 105, Issue 51 https://doi.org/10.1073/pnas.0809045105	journal	December 2008
Genome-wide Analysis of Alternative Pre-mRNA Splicing Ben-Dov, Claudia; Hartmann, Britta; Lundgren, Josefin Journal of Biological Chemistry, Vol. 283, Issue 3 https://doi.org/10.1074/jbc.r700033200	journal	January 2008
Computational Identification of Tissue-Specific Splicing Regulatory Elements in Human Genes from RNA-Seq Data Badr, Eman; ElHefnawi, Mahmoud; Heath, Lenwood S. PLOS ONE, Vol. 11, Issue 11 https://doi.org/10.1371/journal.pone.0166978	journal	November 2016

Similar Records

Computational Analysis of an Evolutionarily Conserved VertebrateMuscle Alternative Splicing Program

Journal Article · Thu Jun 15 00:00:00 EDT 2006 · Nucleic Acids Research · OSTI ID:923004

Developmental regulation of RNA processing by Rbfox proteins

Journal Article · Sun Oct 16 20:00:00 EDT 2016 · Wiley Interdisciplinary Reviews: RNA · OSTI ID:1425412

Prediction of alternatively skipped exons and splicing enhancers from exon junction arrays

Journal Article · Wed Nov 19 19:00:00 EST 2008 · BMC Genomics · OSTI ID:1626472

Related Subjects

60 APPLIED LIFE SCIENCES
Biochemistry & Molecular Biology

A correlation with exon expression approach to identify cis-regulatory elements for tissue-specific alternative splicing

Citation Formats

References (75)

Cited By (31)

Similar Records

Related Subjects