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The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test

BACKGROUND: The evolution of alternatively spliced exons (ASEs) is of primary interest because these exons are suggested to be a major source of functional diversity of proteins. Many exon features have been suggested to affect the evolution of ASEs. However, previous studies have relied on the K(A)...

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Autores principales: Chen, Feng-Chi, Chuang, Trees-Juen
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526763/
https://www.ncbi.nlm.nih.gov/pubmed/16709259
http://dx.doi.org/10.1186/1471-2105-7-259
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author Chen, Feng-Chi
Chuang, Trees-Juen
author_facet Chen, Feng-Chi
Chuang, Trees-Juen
author_sort Chen, Feng-Chi
collection PubMed
description BACKGROUND: The evolution of alternatively spliced exons (ASEs) is of primary interest because these exons are suggested to be a major source of functional diversity of proteins. Many exon features have been suggested to affect the evolution of ASEs. However, previous studies have relied on the K(A)/K(S )ratio test without taking into consideration information sufficiency (i.e., exon length > 75 bp, cross-species divergence > 5%) of the studied exons, leading to potentially biased interpretations. Furthermore, which exon feature dominates the results of the K(A)/K(S )ratio test and whether multiple exon features have additive effects have remained unexplored. RESULTS: In this study, we collect two different datasets for analysis – the ASE dataset (which includes lineage-specific ASEs and conserved ASEs) and the ACE dataset (which includes only conserved ASEs). We first show that information sufficiency can significantly affect the interpretation of relationship between exons features and the K(A)/K(S )ratio test results. After discarding exons with insufficient information, we use a Boolean method to analyze the relationship between test results and four exon features (namely length, protein domain overlapping, inclusion level, and exonic splicing enhancer (ESE) frequency) for the ASE dataset. We demonstrate that length and protein domain overlapping are dominant factors, and they have similar impacts on test results of ASEs. In addition, despite the weak impacts of inclusion level and ESE motif frequency when considered individually, combination of these two factors still have minor additive effects on test results. However, the ACE dataset shows a slightly different result in that inclusion level has a marginally significant effect on test results. Lineage-specific ASEs may have contributed to the difference. Overall, in both ASEs and ACEs, protein domain overlapping is the most dominant exon feature while ESE frequency is the weakest one in affecting test results. CONCLUSION: The proposed method can easily find additive effects of individual or multiple factors on the K(A)/K(S )ratio test results of exons. Therefore, the system can analyze complex conditions in evolution where multiple features are involved. More factors can also be added into the system to extend the scope of evolutionary analysis of exons. In addition, our method may be useful when orthologous exons can not be found for the K(A)/K(S )ratio test.
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spelling pubmed-15267632006-08-07 The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test Chen, Feng-Chi Chuang, Trees-Juen BMC Bioinformatics Methodology Article BACKGROUND: The evolution of alternatively spliced exons (ASEs) is of primary interest because these exons are suggested to be a major source of functional diversity of proteins. Many exon features have been suggested to affect the evolution of ASEs. However, previous studies have relied on the K(A)/K(S )ratio test without taking into consideration information sufficiency (i.e., exon length > 75 bp, cross-species divergence > 5%) of the studied exons, leading to potentially biased interpretations. Furthermore, which exon feature dominates the results of the K(A)/K(S )ratio test and whether multiple exon features have additive effects have remained unexplored. RESULTS: In this study, we collect two different datasets for analysis – the ASE dataset (which includes lineage-specific ASEs and conserved ASEs) and the ACE dataset (which includes only conserved ASEs). We first show that information sufficiency can significantly affect the interpretation of relationship between exons features and the K(A)/K(S )ratio test results. After discarding exons with insufficient information, we use a Boolean method to analyze the relationship between test results and four exon features (namely length, protein domain overlapping, inclusion level, and exonic splicing enhancer (ESE) frequency) for the ASE dataset. We demonstrate that length and protein domain overlapping are dominant factors, and they have similar impacts on test results of ASEs. In addition, despite the weak impacts of inclusion level and ESE motif frequency when considered individually, combination of these two factors still have minor additive effects on test results. However, the ACE dataset shows a slightly different result in that inclusion level has a marginally significant effect on test results. Lineage-specific ASEs may have contributed to the difference. Overall, in both ASEs and ACEs, protein domain overlapping is the most dominant exon feature while ESE frequency is the weakest one in affecting test results. CONCLUSION: The proposed method can easily find additive effects of individual or multiple factors on the K(A)/K(S )ratio test results of exons. Therefore, the system can analyze complex conditions in evolution where multiple features are involved. More factors can also be added into the system to extend the scope of evolutionary analysis of exons. In addition, our method may be useful when orthologous exons can not be found for the K(A)/K(S )ratio test. BioMed Central 2006-05-19 /pmc/articles/PMC1526763/ /pubmed/16709259 http://dx.doi.org/10.1186/1471-2105-7-259 Text en Copyright © 2006 Chen and Chuang; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Methodology Article
Chen, Feng-Chi
Chuang, Trees-Juen
The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test
title The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test
title_full The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test
title_fullStr The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test
title_full_unstemmed The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test
title_short The effects of multiple features of alternatively spliced exons on the K(A)/K(S )ratio test
title_sort effects of multiple features of alternatively spliced exons on the k(a)/k(s )ratio test
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526763/
https://www.ncbi.nlm.nih.gov/pubmed/16709259
http://dx.doi.org/10.1186/1471-2105-7-259
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