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Determining Coding CpG Islands by Identifying Regions Significant for Pattern Statistics on Markov Chains

Singer, Meromit and Engström, Alexander and Schönhuth, Alexander and Pachter, Lior (2011) Determining Coding CpG Islands by Identifying Regions Significant for Pattern Statistics on Markov Chains. Statistical Applications in Genetics and Molecular Biology, 10 (1). Art. No. 43. ISSN 2194-6302. https://resolver.caltech.edu/CaltechAUTHORS:20170306-100428893

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Abstract

Recent experimental and computational work confirms that CpGs can be unmethylated inside coding exons, thereby showing that codons may be subjected to both genomic and epigenomic constraint. It is therefore of interest to identify coding CpG islands (CCGIs) that are regions inside exons enriched for CpGs. The difficulty in identifying such islands is that coding exons exhibit sequence biases determined by codon usage and constraints that must be taken into account. We present a method for finding CCGIs that showcases a novel approach we have developed for identifying regions of interest that are significant (with respect to a Markov chain) for the counts of any pattern. Our method begins with the exact computation of tail probabilities for the number of CpGs in all regions contained in coding exons, and then applies a greedy algorithm for selecting islands from among the regions. We show that the greedy algorithm provably optimizes a biologically motivated criterion for selecting islands while controlling the false discovery rate. We applied this approach to the human genome (hg18) and annotated CpG islands in coding exons. The statistical criterion we apply to evaluating islands reduces the number of false positives in existing annotations, while our approach to defining islands reveals significant numbers of undiscovered CCGIs in coding exons. Many of these appear to be examples of functional epigenetic specialization in coding exons.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.2202/1544-6115.1677DOIArticle
https://www.degruyter.com/view/j/sagmb.2011.10.issue-1/1544-6115.1677/1544-6115.1677.xmlPublisherArticle
Additional Information:© 2011 by Walter de Gruyter GmbH.
Subject Keywords:Markov chains; pattern statistics; CpG islands; genomics
Issue or Number:1
Record Number:CaltechAUTHORS:20170306-100428893
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170306-100428893
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74769
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:06 Mar 2017 18:09
Last Modified:03 Oct 2019 16:42

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