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Title:
Identifying and characterising key alternative splicing events in Drosophila development | BMC Genomics
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Background In complex Metazoans a given gene frequently codes for multiple protein isoforms, through processes such as alternative splicing. Large scale functional annotation of these isoforms is a key challenge for functional genomics. This annotation gap is increasing with the large numbers of multi transcript genes being identified by technologies such as RNASeq. Furthermore attempts to characterise the functions of splicing in an organism are complicated by the difficulty in distinguishing functional isoforms from those produced by splicing errors or transcription noise. Tools to help prioritise candidate isoforms for testing are largely absent. Results In this study we implement a Time-course Switch (TS) score for ranking isoforms by their likelihood of producing additional functions based on their developmental expression profiles, as reported by modENCODE. The TS score allows us to better investigate functional roles of different isoforms expressed in multi transcript genes. From this analysis, we find that isoforms with high TS scores have sequence feature changes consistent with more deterministic splicing and functional changes and tend to gain domains or whole exons which could carry additional functions. Furthermore these functions appear to be particularly important for essential regulatory roles, establishing functional isoform switching as key for regulatory processes. Based on the TS score we develop a Transcript Annotations Pipeline for Alternative Splicing (TAPAS) that identifies functional neighbourhoods of potentially interesting isoforms. Conclusions We have identified a subset of protein isoforms which appear to have high functional significance, particularly in regulation. This has been made possible through the development of novel methods that make use of transcript expression profiles. The methods and analyses we present here represent important first steps in the development of tools to address the near complete lack of isoform specific function annotation. In turn the tools allow us to better characterise the regulatory functions of alternative splicing in more detail.
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Keywords {🔍}
genes, isoforms, isoform, gene, expression, protein, functional, score, splicing, primary, transcript, hights, alternative, high, domain, article, secondary, scores, sequence, function, functions, fig, specific, database, methods, minor, enrichment, pubmed, query, goss, essential, profiles, important, tapas, terms, development, res, analysis, nucleic, acids, annotation, level, low, similarity, cluster, data, events, multi, proteins, enriched,
Topics {✒️}
eu-fp7-systems microscopy noe uk/pub/gene3d_data/current_release/tapas cysteine-rich zinc-finger literature intron retention mann–whitney rank test �nuclear hormone receptor” transcription factor regulation open access license ecr isoform-specific mutations complex multicellular organisms fast gapped-read alignment minor splice variants protein coding sequence mis-splicing event compared high-ts genes annotated full access nuclear receptor coactivators anti-correlated gene pairs alternative transcription initiation alternatively high-ts genes alternative splice isoforms large-scale evaluation ligand activation act nuclear hormone receptors ligand binding [32] phorbol ester binding high-ts genes relative primary/minor isoform pair dna binding high-ts genes enrichment high-ts genes tend privacy choices/manage cookies transcription factors domains high-ts genes compared article download pdf yeast evolve slowly carney ge identifies functional neighbourhoods functional interaction networks splice variants mol genet genomics high functional significance find high-ts genes sequence specific manner identified lig_nrbox motifs tissue-specific splicing profile–profile comparisons protein sequence divergence secondary isoform represents alternative splicing events
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- Alternative splicing regulation of telomerase: a new paradigm?
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headline:Identifying and characterising key alternative splicing events in Drosophila development
description:In complex Metazoans a given gene frequently codes for multiple protein isoforms, through processes such as alternative splicing. Large scale functional annotation of these isoforms is a key challenge for functional genomics. This annotation gap is increasing with the large numbers of multi transcript genes being identified by technologies such as RNASeq. Furthermore attempts to characterise the functions of splicing in an organism are complicated by the difficulty in distinguishing functional isoforms from those produced by splicing errors or transcription noise. Tools to help prioritise candidate isoforms for testing are largely absent. In this study we implement a Time-course Switch (TS) score for ranking isoforms by their likelihood of producing additional functions based on their developmental expression profiles, as reported by modENCODE. The TS score allows us to better investigate functional roles of different isoforms expressed in multi transcript genes. From this analysis, we find that isoforms with high TS scores have sequence feature changes consistent with more deterministic splicing and functional changes and tend to gain domains or whole exons which could carry additional functions. Furthermore these functions appear to be particularly important for essential regulatory roles, establishing functional isoform switching as key for regulatory processes. Based on the TS score we develop a Transcript Annotations Pipeline for Alternative Splicing (TAPAS) that identifies functional neighbourhoods of potentially interesting isoforms. We have identified a subset of protein isoforms which appear to have high functional significance, particularly in regulation. This has been made possible through the development of novel methods that make use of transcript expression profiles. The methods and analyses we present here represent important first steps in the development of tools to address the near complete lack of isoform specific function annotation. In turn the tools allow us to better characterise the regulatory functions of alternative splicing in more detail.
datePublished:2015-08-16T00:00:00Z
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Gene Ontology
Alternative Splice
Nuclear Hormone Receptor
Intron Retention
Domain Assignment
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general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
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headline:Identifying and characterising key alternative splicing events in Drosophila development
description:In complex Metazoans a given gene frequently codes for multiple protein isoforms, through processes such as alternative splicing. Large scale functional annotation of these isoforms is a key challenge for functional genomics. This annotation gap is increasing with the large numbers of multi transcript genes being identified by technologies such as RNASeq. Furthermore attempts to characterise the functions of splicing in an organism are complicated by the difficulty in distinguishing functional isoforms from those produced by splicing errors or transcription noise. Tools to help prioritise candidate isoforms for testing are largely absent. In this study we implement a Time-course Switch (TS) score for ranking isoforms by their likelihood of producing additional functions based on their developmental expression profiles, as reported by modENCODE. The TS score allows us to better investigate functional roles of different isoforms expressed in multi transcript genes. From this analysis, we find that isoforms with high TS scores have sequence feature changes consistent with more deterministic splicing and functional changes and tend to gain domains or whole exons which could carry additional functions. Furthermore these functions appear to be particularly important for essential regulatory roles, establishing functional isoform switching as key for regulatory processes. Based on the TS score we develop a Transcript Annotations Pipeline for Alternative Splicing (TAPAS) that identifies functional neighbourhoods of potentially interesting isoforms. We have identified a subset of protein isoforms which appear to have high functional significance, particularly in regulation. This has been made possible through the development of novel methods that make use of transcript expression profiles. The methods and analyses we present here represent important first steps in the development of tools to address the near complete lack of isoform specific function annotation. In turn the tools allow us to better characterise the regulatory functions of alternative splicing in more detail.
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Gene Ontology
Alternative Splice
Nuclear Hormone Receptor
Intron Retention
Domain Assignment
Life Sciences
general
Microarrays
Proteomics
Animal Genetics and Genomics
Microbial Genetics and Genomics
Plant Genetics and Genomics
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