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

Journal Article · · BMC Genomics
 [1];  [2];  [3]
  1. Univ. of Colorado, Denver, CO (United States). Colorado School of Public Health. Dept. of Biostatistics and Informatics; DOE/OSTI
  2. Univ. of Sydney, NSW (Australia). Sydney Bioinformatics. School of Mathematics and Statistics
  3. Univ. of California, San Francisco, CA (United States). Dept. of Epidemiology and Biostatistics
Background: Alternative splicing of exons in a pre-mRNA transcript is an important mechanism which contributes to protein diversity in human. Arrays for detecting alternative splicing are available using several different probe designs, including those based on exon-junctions. In this work, we introduce a new method for predicting alternatively skipped exons from exon-junction arrays. Predictions based on our method are compared against controls and their sequences are analyzed to identify motifs important for regulating alternative splicing. Results: Our comparison of several alternative methods shows that an exon-skipping score based on neighboring junctions best discriminates between positive and negative controls. Sequence analysis of our predicted exons confirms the presence of known splicing regulatory sequences. In addition, we also derive a set of development-related alternatively spliced genes based on fetal versus adult tissue comparisons and find that our predictions are consistent with their functional annotations. Ab initio motif finding algorithms are applied to identify several motifs that may be relevant for splicing during development. Conclusion: This work describes a new method for analyzing exon-junction arrays, identifies sequence motifs that are specific for alternative and constitutive splicing and suggests a role for several known splicing factors and their motifs in developmental regulation.
Research Organization:
Univ. of California, San Francisco, CA (United States)
Sponsoring Organization:
Sloan Foundation; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI ID:
1626472
Journal Information:
BMC Genomics, Journal Name: BMC Genomics Journal Issue: 1 Vol. 9; ISSN 1471-2164
Publisher:
SpringerCopyright Statement
Country of Publication:
United States
Language:
English

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Computational identification of tissue-specific alternative splicing elements in mouse genes from RNA-Seq journal August 2010
Systematic Spatial Bias in DNA Microarray Hybridization Is Caused by Probe Spot Position-Dependent Variability in Lateral Diffusion journal August 2011
Large-Scale Profiling of RBP-circRNA Interactions from Public CLIP-Seq Datasets journal November 2019
Compressed Weighted de Bruijn Graphs text January 2021
Role of splice variants in the metastatic progression of prostate cancer journal July 2012