cpg island mapping by epigenome predictioncpg岛映射的表观基因组预测.pdfVIP

CpG Island Mapping by Epigenome Prediction 1* ¨ 2 2 1 Christoph Bock , Jorn Walter , Martina Paulsen , Thomas Lengauer ¨ ¨ ¨ ¨ 1 Max-Planck-Institut fur Informatik, Saarbrucken, Germany, 2 Genetik/Epigenetik, Universitat des Saarlandes, Saarbrucken, Germany CpG islands were originally identified by epigenetic and functional properties, namely, absence of DNA methylation and frequent promoter association. However, this concept was quickly replaced by simple DNA sequence criteria, which allowed for genome-wide annotation of CpG islands in the absence of large-scale epigenetic datasets. Although widely used, the current CpG island criteria incur significant disadvantages: (1) reliance on arbitrary threshold parameters that bear little biological justification, (2) failure to account for widespread heterogeneity among CpG islands, and (3) apparent lack of specificity when applied to the human genome. This study is driven by the idea that a quantitative score of ‘‘CpG island strength’’ that incorporates epigenetic and functional aspects can help resolve these issues. We construct an epigenome prediction pipeline that links the DNA sequence of CpG islands to their epigenetic states, including DNA methylation, histone modifications, and chromatin accessibility. By training support vector machines on epigenetic data for CpG islands on human Chromosomes 21 and 22, we identify informative DNA attributes that correlate with open versus compact chromatin structures. These DNA attributes are used to predict the epigenetic states of all CpG islands genome-wide. Combining predictions for multiple epigenetic features, we estimate the inherent CpG island strengt