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Christopher Burge. Rothman, Craig Jeremy Massachusetts Institute of Technology. Biological Engineering Division. Massachusetts Institute of Technology. Department of Biological Engineering 2008-01-10T16:01:20Z 2008-01-10T16:01:20Z 2007 2007 http://hdl.handle.net/1721.1/39920 182622079 Thesis (M. Eng.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007. Includes bibliographical references (p. 53-57). Alternative splicing is involved in numerous cellular functions and is often disrupted and involved in disease. Previous research has identified methods to distinguish alternative conserved exons (ACEs) in human and mouse. However, the cellular machinery, the spliceosome, does not use comparative genomics to decide when to include and when to exclude an exon. Human RefSeq exons obtained from the University of California Santa Cruz (UCSC) genome browser were analyzed for tissue-specific skipping. Expressed sequence tags (ESTs) were aligned to exons and their tissue of origin and histology were identified. ACEs were also identified as a subset of the skipped exons. About 18% of the exons were identified as tissue-specifically skipped in one of sixteen different tissues at four stringency levels. The different datasets were analyzed for both general features such as exon and intron length, splice site strength, base composition, conservation, modularity, and susceptibility to nonsense-mediated mRNA decay caused by skipping. Cis-element motifs that might bind protein factors that affect splicing were identified using overrepresentation analysis and conserved occurrence rate between human and mouse. (cont.) Tissue-specific skipped exons were then classified with both a decision-tree based classifier (Random ForestsTM) and a support vector machine. Classification results were better for tissue-specific skipped exons vs. constitutive exons than for tissue-specific skipped exons vs. exons skipped in other tissues. by Craig Jeremy Rothman. M.Eng. 57 p. eng Massachusetts Institute of Technology MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided. http://dspace.mit.edu/handle/1721.1/7582 Biological Engineering Division. Tissue-specific classification of alternatively spliced human exons Thesis application/pdf false Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="4255cf7a-16ed-4f16-b60e-f6c6a2e44e35"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Language>eng</Language> <Title>Tissue-specific classification of alternatively spliced human exons</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2007</PublicationDate> <Authors> <Author> <DisplayName>Rothman, Craig Jeremy</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://dspace.mit.edu/handle/1721.1/7582</License> <Keyword>Biological Engineering Division.</Keyword> <Abstract>Alternative splicing is involved in numerous cellular functions and is often disrupted and involved in disease. Previous research has identified methods to distinguish alternative conserved exons (ACEs) in human and mouse. However, the cellular machinery, the spliceosome, does not use comparative genomics to decide when to include and when to exclude an exon. Human RefSeq exons obtained from the University of California Santa Cruz (UCSC) genome browser were analyzed for tissue-specific skipping. Expressed sequence tags (ESTs) were aligned to exons and their tissue of origin and histology were identified. ACEs were also identified as a subset of the skipped exons. About 18% of the exons were identified as tissue-specifically skipped in one of sixteen different tissues at four stringency levels. The different datasets were analyzed for both general features such as exon and intron length, splice site strength, base composition, conservation, modularity, and susceptibility to nonsense-mediated mRNA decay caused by skipping. Cis-element motifs that might bind protein factors that affect splicing were identified using overrepresentation analysis and conserved occurrence rate between human and mouse.</Abstract> <Abstract>(cont.) Tissue-specific skipped exons were then classified with both a decision-tree based classifier (Random ForestsTM) and a support vector machine. Classification results were better for tissue-specific skipped exons vs. constitutive exons than for tissue-specific skipped exons vs. exons skipped in other tissues.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>