CpG island methylation in human lymphocytes is highly correlated with DNA sequence, repeats, and predicted DNA structure

PLoS Genetics
Christoph BockJörn Walter

Abstract

CpG island methylation plays an important role in epigenetic gene control during mammalian development and is frequently altered in disease situations such as cancer. The majority of CpG islands is normally unmethylated, but a sizeable fraction is prone to become methylated in various cell types and pathological situations. The goal of this study is to show that a computational epigenetics approach can discriminate between CpG islands that are prone to methylation from those that remain unmethylated. We develop a bioinformatics scoring and prediction method on the basis of a set of 1,184 DNA attributes, which refer to sequence, repeats, predicted structure, CpG islands, genes, predicted binding sites, conservation, and single nucleotide polymorphisms. These attributes are scored on 132 CpG islands across the entire human Chromosome 21, whose methylation status was previously established for normal human lymphocytes. Our results show that three groups of DNA attributes, namely certain sequence patterns, specific DNA repeats, and a particular DNA structure, are each highly correlated with CpG island methylation (correlation coefficients of 0.64, 0.66, and 0.49, respectively). We predicted, and subsequently experimentally examined...Continue Reading

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Methods Mentioned

BETA
deamination
PCR

Software Mentioned

WEKA
RepeatMasker
Excel
R
AdaBoost
UCSC Genome Browser
LIBSVM
BiQ Analyzer
WEKA package
Ensembl

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