title: Predicting CpG methylation levels by integrating Infinium HumanMethylation450 BeadChip array data.
abstract: The Infinium HumanMethylation450 BeadChip array, referred as 450K array hereinafter, has been widely adopted as an affordable technique to determine DNA methylation. Tens of thousands of data have been generated on diverse cell types and patient tissues, which have provided great insight into understanding the crucial roles of epigenetic modifications in many biological processes and diseases. The limitation of this technique is its coverage, which measures methylation levels of about 450,000 CpGs, accounting for about 1.6% of all CpGs in the human genome. In the present study we developed and compared computational models to significantly expand the coverage of Illumina 450K (~11 folds). Using the whole genome bisulfite sequencing and Illumina 450K data in the human H1 embryonic stem cell, we showed that the predicted and measured methylation levels were well correlated. Our proposed model showed superior prediction accuracies compared to the existing methods on the same dataset. When applied to predict the DNA methylome on other cells, our proposed model achieved comparable performance in cross-validations, which indicates the generalizibility of the method. Our method would thus be invaluable to maximize the usage of the existing data.
authors.affiliation: School of Automation Engineering, University of Electronic Science and Technology of China, Chengdu, China; Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA. Electronic address: shicaifan@uestc.edu.cn.
authors.forename: Shicai
authors.initials: S
authors.lastname: Fan
authors.affiliation: School of Automation Engineering, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
authors.forename: Rizi
authors.initials: R
authors.lastname: Ai
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
authors.forename: Mengchi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA. Electronic address: wei-wang@ucsd.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D016015:Logistic Models; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D060388:Support Vector Machine
keywords: 450K array data; CpG loci; DNA methylation; Prediction