Journal
BMC GENOMICS
Volume 15, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1471-2164-15-51
Keywords
HumanMethylation450K BeadChip; SNPs; INDELS; Repetitive regions of DNA; SNP arrays; HM450K bead array; Epigenome-wide association studies; EWAS; Cancer; Epigenetics
Funding
- NICTA
- Australian Government
- Australian Research Council through the ICT Centre of Excellence program
- Victorian Cancer Agency
- National Health and Medical Research Council
- My Room and the Children's Cancer Centre Foundation
- Victorian Government's Operational Infrastructure Support Program
- Department of Health and Aging, Australia
- NHMRC [1047581]
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Background: The Illumina HumanMethylation450 BeadChip (HM450K) measures the DNA methylation of 485,512 CpGs in the human genome. The technology relies on hybridization of genomic fragments to probes on the chip. However, certain genomic factors may compromise the ability to measure methylation using the array such as single nucleotide polymorphisms (SNPs), small insertions and deletions (INDELs), repetitive DNA, and regions with reduced genomic complexity. Currently, there is no clear method or pipeline for determining which of the probes on the HM450K bead array should be retained for subsequent analysis in light of these issues. Results: We comprehensively assessed the effects of SNPs, INDELs, repeats and bisulfite induced reduced genomic complexity by comparing HM450K bead array results with whole genome bisulfite sequencing. We determined which CpG probes provided accurate or noisy signals. From this, we derived a set of high-quality probes that provide unadulterated measurements of DNA methylation. Conclusions: Our method significantly reduces the risk of false discoveries when using the HM450K bead array, while maximising the power of the array to detect methylation status genome-wide. Additionally, we demonstrate the utility of our method through extraction of biologically relevant epigenetic changes in prostate cancer.
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