Introduction

DNA methylation signatures in rheumatoid arthritis (RA) have been identified in fibroblast-like synoviocytes (FLS) with Illumina HumanMethylation450 array. Since <2% of CpG sites are covered by the Illumina 450K array and whole genome bisulfite sequencing is still too expensive for many samples, computationally predicting DNA methylation levels based on 450K data would be valuable to discover more RA-related genes.We developed a computational model that is trained on 14 tissues with both whole genome bisulfite sequencing and 450K array data. This model integrates information derived from the similarity of local methylation pattern between tissues, the methylation information of flanking CpG sites and the methylation tendency of flanking DNA sequences. The predicted and measured methylation values were highly correlated with a Pearson correlation coefficient of 0.9 in leave-one-tissue-out cross-validations. Importantly, the majority (76%) of the top 10% differentially methylated loci among the 14 tissues was correctly detected using the predicted methylation values. Applying this model to 450K data of RA, osteoarthritis and normal FLS, we successfully expanded the coverage of CpG sites 18.5-fold and accounts for about 30% of all the CpGs in the human genome. By integrative omics study, we identified genes and pathways tightly related to RA pathogenesis, among which 12 genes were supported by triple evidences, including 6 genes already known to perform specific roles in RA and 6 genes as new potential therapeutic targets.The source code, required data for prediction, and demo data for test are freely available at: http://wanglab.ucsd.edu/star/LR450K/ CONTACT: wei-wang@ucsd.edu or gfirestein@ucsd.eduSupplementary data are available at Bioinformatics online.

Publications

  1. Computationally expanding infinium HumanMethylation450 BeadChip array data to reveal distinct DNA methylation patterns of rheumatoid arthritis.
    Cite this
    Fan S, Li C, Ai R, Wang M, Firestein GS, Wang W, 2016-06-01 - Bioinformatics (Oxford, England)

Credits

  1. Shicai Fan
    Developer

    School of Automation Engineering, University of Electronic Science and Technology of China, China

  2. Chengzhe Li
    Developer

    School of Automation Engineering, University of Electronic Science and Technology of China, China

  3. Rizi Ai
    Developer

  4. Mengchi Wang
    Developer

  5. Gary S Firestein
    Developer

    Division of Rheumatology, Allergy and Immunology, United States of America

  6. Wei Wang
    Investigator

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Summary
AccessionBT001129
Tool TypeApplication
Category
PlatformsLinux/Unix
TechnologiesR
User InterfaceTerminal Command Line
Download Count0
Submitted ByWei Wang