{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T10:40:02Z","timestamp":1738924802143,"version":"3.37.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"S1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alternative splicing (AS) is an important regulatory mechanism for gene expression and protein diversity in eukaryotes. Previous studies have demonstrated that it can be causative for, or specific to splicing-related diseases. Understanding the regulation of AS will be helpful for diagnostic efforts and drug discoveries on those splicing-related diseases. As a novel exon-centric microarray platform, exon array enables a comprehensive analysis of AS by investigating the expression of known and predicted exons. Identifying of AS events from exon array has raised much attention, however, new and powerful algorithms for exon array data analysis are still absent till now.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we considered identifying of AS events in the framework of variable selection and developed a regression method for AS detection (REMAS). Firstly, features of alternatively spliced exons were scaled by reasonably defined variables. Secondly, we designed a hierarchical model which can represent gene structure and transcriptional influence to exons, and the lasso type penalties were introduced in calculation because of huge variable size. Thirdly, an iterative two-step algorithm was developed to select alternatively spliced genes and exons. To avoid negative effects introduced by small sample size, we ranked genes as parameters indicating their AS capabilities in an iterative manner. After that, both simulation and real data evaluation showed that REMAS could efficiently identify potential AS events, some of which had been validated by RT-PCR or supported by literature evidence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>As a new lasso regression algorithm based on hierarchical model, REMAS has been demonstrated as a reliable and effective method to identify AS events from exon array data.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2105-10-s1-s18","type":"journal-article","created":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T20:04:49Z","timestamp":1233345889000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["REMAS: a new regression model to identify alternative splicing events from exon array data"],"prefix":"10.1186","volume":"10","author":[{"given":"Hao","family":"Zheng","sequence":"first","affiliation":[]},{"given":"Xingyi","family":"Hang","sequence":"additional","affiliation":[]},{"given":"Ji","family":"Zhu","sequence":"additional","affiliation":[]},{"given":"Minping","family":"Qian","sequence":"additional","affiliation":[]},{"given":"Wubin","family":"Qu","sequence":"additional","affiliation":[]},{"given":"Chenggang","family":"Zhang","sequence":"additional","affiliation":[]},{"given":"Minghua","family":"Deng","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"issue":"1","key":"3201_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/nsmb0104-4","volume":"11","author":"B Davletov","year":"2004","unstructured":"Davletov B, Jimenez JL: Sculpting a domain by splicing. Nature Structural & Molecular Biology. 2004, 11 (1): 4-5. 10.1038\/nsmb0104-4.","journal-title":"Nature Structural & Molecular Biology"},{"issue":"10","key":"3201_CR2","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/nrg2164","volume":"8","author":"GS Wang","year":"2007","unstructured":"Wang GS, Cooper TA: Splicing in disease: disruption of the splicing code and the decoding machinery. Nature Reviews Genetics. 2007, 8 (10): 749-761. 10.1038\/nrg2164.","journal-title":"Nature Reviews Genetics"},{"key":"3201_CR3","doi-asserted-by":"crossref","unstructured":"Yeo GWM: Splicing regulators: targets and drugs. Genome Biology. 2005, 6 (12):","DOI":"10.1186\/gb-2005-6-12-240"},{"issue":"1","key":"3201_CR4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/ng0102-13","volume":"30","author":"B Modrek","year":"2002","unstructured":"Modrek B, Lee C: A genomic view of alternative splicing. Nature Genetics. 2002, 30 (1): 13-19. 10.1038\/ng0102-13.","journal-title":"Nature Genetics"},{"issue":"3","key":"3201_CR5","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1089\/omi.2006.10.344","volume":"10","author":"M Cuperlovic-Culf","year":"2006","unstructured":"Cuperlovic-Culf M, Belacel N, Culf AS, Ouellette RJ: Microarray analysis of alternative splicing. Omics-a Journal of Integrative Biology. 2006, 10 (3): 344-357. 10.1089\/omi.2006.10.344.","journal-title":"Omics-a Journal of Integrative Biology"},{"issue":"5569","key":"3201_CR6","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1126\/science.1069415","volume":"296","author":"TA Clark","year":"2002","unstructured":"Clark TA, Sugnet CW, Ares M: Genomewide analysis of mRNA processing in yeast using splicing-specific microarrays. Science. 2002, 296 (5569): 907-910. 10.1126\/science.1069415.","journal-title":"Science"},{"issue":"4","key":"3201_CR7","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/nbt0402-353","volume":"20","author":"JM Yeakley","year":"2002","unstructured":"Yeakley JM, Fan JB, Doucet D, Luo L, Wickham E, Ye Z, Chee MS, Fu XD: Profiling alternative splicing on fiber-optic arrays. Nature Biotechnology. 2002, 20 (4): 353-358. 10.1038\/nbt0402-353.","journal-title":"Nature Biotechnology"},{"issue":"5653","key":"3201_CR8","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1126\/science.1090100","volume":"302","author":"JM Johnson","year":"2003","unstructured":"Johnson JM, Castle J, Garrett-Engele P, Kan ZY, Loerch PM, Armour CD, Santos R, Schadt EE, Stoughton R, Shoemaker DD: Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science. 2003, 302 (5653): 2141-2144. 10.1126\/science.1090100.","journal-title":"Science"},{"issue":"6","key":"3201_CR9","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1016\/j.molcel.2004.12.004","volume":"16","author":"Q Pan","year":"2004","unstructured":"Pan Q, Shai O, Misquitta C, Zhang W, Saltzman AL, Mohammad N, Babak T, Siu H, Hughes TR, Morris QD: Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform. Molecular Cell. 2004, 16 (6): 929-941. 10.1016\/j.molcel.2004.12.004.","journal-title":"Molecular Cell"},{"issue":"8","key":"3201_CR10","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/ng1610","volume":"37","author":"J Ule","year":"2005","unstructured":"Ule J, Ule A, Spencer J, Williams A, Hu JS, Cline M, Wang H, Clark T, Fraser C, Ruggiu M: Nova regulates brain-specific splicing to shape the synapse. Nature Genetics. 2005, 37 (8): 844-852. 10.1038\/ng1610.","journal-title":"Nature Genetics"},{"issue":"5","key":"3201_CR11","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1093\/bioinformatics\/btk028","volume":"22","author":"O Shai","year":"2006","unstructured":"Shai O, Morris QD, Blencowe BJ, Frey BJ: Inferring global levels of alternative splicing isoforms using a generative model of microarray data. Bioinformatics. 2006, 22 (5): 606-613. 10.1093\/bioinformatics\/btk028.","journal-title":"Bioinformatics"},{"key":"3201_CR12","doi-asserted-by":"publisher","first-page":"I107","DOI":"10.1093\/bioinformatics\/bti1010","volume":"21","author":"MS Cline","year":"2005","unstructured":"Cline MS, Blume J, Cawley S, Clark TA, Hu JS, Lu G, Salomonis N, Wang H, Williams A: ANOSVA: a statistical method for detecting splice variation from expression data. Bioinformatics. 2005, 21: I107-I115. 10.1093\/bioinformatics\/bti1010.","journal-title":"Bioinformatics"},{"key":"3201_CR13","doi-asserted-by":"crossref","unstructured":"Le K, Mitsouras K, Roy M, Wang Q, Xu Q, Nelson SF, Lee C: Detecting tissue-specific regulation of alternative splicing as a qualitative change in microarray data. Nucleic Acids Research. 2004, 32 (22):","DOI":"10.1093\/nar\/gnh173"},{"issue":"4","key":"3201_CR14","doi-asserted-by":"publisher","first-page":"R64","DOI":"10.1186\/gb-2007-8-4-r64","volume":"8","author":"TA Clark","year":"2007","unstructured":"Clark TA, Schweitzer AC, Chen TX, Staples MK, Lu G, Wang H, Williams A, Blume JE: Discovery of tissue-specific exons using comprehensive human exon microarrays. Genome Biology. 2007, 8 (4): R64-10.1186\/gb-2007-8-4-r64.","journal-title":"Genome Biology"},{"issue":"12","key":"3201_CR15","doi-asserted-by":"publisher","first-page":"5635","DOI":"10.1158\/0008-5472.CAN-06-2869","volume":"67","author":"PJ French","year":"2007","unstructured":"French PJ, Peeters J, Horsman S, Duijm E, Siccama I, Bent van den MJ, Luider TM, Kros JM, Spek van der P, Smitt PAS: Identification of differentially regulated splice variants and novel exons in glial brain tumors using exon expression arrays. Cancer Research. 2007, 67 (12): 5635-5642. 10.1158\/0008-5472.CAN-06-2869.","journal-title":"Cancer Research"},{"key":"3201_CR16","volume-title":"Bmc Genomics","author":"PJ Gardina","year":"2006","unstructured":"Gardina PJ, Clark TA, Shimada B, Staples MK, Yang Q, Veitch J, Schweitzer A, Awad T, Sugnet C, Dee S: Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array. Bmc Genomics. 2006, 7:"},{"issue":"1","key":"3201_CR17","doi-asserted-by":"publisher","first-page":"e88","DOI":"10.1371\/journal.pone.0000088","volume":"1","author":"Y Xing","year":"2006","unstructured":"Xing Y, Kapur K, Wong WH: Probe Selection and Expression Index Computation of Affymetrix Exon Arrays. PLoS ONE. 2006, 1 (1): e88-10.1371\/journal.pone.0000088.","journal-title":"PLoS ONE"},{"key":"3201_CR18","doi-asserted-by":"crossref","unstructured":"Kapur K, Xing Y, Ouyang Z, Wong WH: Exon arrays provide accurate assessments of gene expression. Genome Biology. 2007, 8 (5):","DOI":"10.1186\/gb-2007-8-5-r82"},{"issue":"1","key":"3201_CR19","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1111\/j.2517-6161.1996.tb02080.x","volume":"58","author":"R Tibshirani","year":"1996","unstructured":"Tibshirani R: Regression shrinkage and selection via the Lasso. Journal of the Royal Statistical Society Series B-Methodological. 1996, 58 (1): 267-288.","journal-title":"Journal of the Royal Statistical Society Series B-Methodological"},{"issue":"1","key":"3201_CR20","doi-asserted-by":"publisher","first-page":"R2","DOI":"10.1186\/gb-2006-7-1-r2","volume":"7","author":"D Anastassiou","year":"2006","unstructured":"Anastassiou D, Liu H, Varadan V: Variable window binding for mutually exclusive alternative splicing. Genome Biology. 2006, 7 (1): R2-10.1186\/gb-2006-7-1-r2.","journal-title":"Genome Biology"},{"issue":"(Database issue","key":"3201_CR21","first-page":"D501","volume":"33","author":"KD Pruitt","year":"2005","unstructured":"Pruitt KD, Tatusova T, Maglott DR: NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucl Acids Res. 2005, 33 ((Database issue)): D501-504.","journal-title":"Nucl Acids Res"},{"key":"3201_CR22","volume-title":"RNA","author":"Y Xing","year":"2008","unstructured":"Xing Y, Stoilov P, Kapur K, Han A, Jiang H, Shen S, Black DL, Wong WH: MADS: A new and improved method for analysis of differential alternative splicing by exon-tiling microarrays. RNA. 2008, rna.1070208."}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1471-2105-10-S1-S18.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T09:34:03Z","timestamp":1738920843000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/1471-2105-10-S1-S18"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1]]},"references-count":22,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2009,1]]}},"alternative-id":["3201"],"URL":"https:\/\/doi.org\/10.1186\/1471-2105-10-s1-s18","relation":{},"ISSN":["1471-2105"],"issn-type":[{"type":"electronic","value":"1471-2105"}],"subject":[],"published":{"date-parts":[[2009,1]]},"assertion":[{"value":"30 January 2009","order":1,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"S18"}}