Journal Article

Reducing the risk of false discovery enabling identification of biologically significant genome-wide methylation status using the HumanMethylation450 array

Pedersen, John S, Chatterton, Zac, Naeem, Haroon, Macintyre, Geoff, Wong, Nicholas C, Corcoran, Niall M, Hong, Matthew K H, Hovens, Christopher M

2014

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V
• Subject: Animal Genetics and Genomics / Biomedical and Life Sciences / Biotechnology industry / Cancer / CpG Islands / Deoxyribonucleic acid / DNA / DNA Methylation / Epigenetic inheritance / Gene Deletion / Genetic aspects / Genome, Human / Genomics / Genotype / High-Throughput Nucleotide Sequencing / Human and rodent genomics / Humans / Life Sciences / Measurement / Methodology / Methodology Article / Methods / Microarrays / Microbial Genetics and Genomics / Mutagenesis, Insertional / Oligonucleotide Array Sequence Analysis / Oncology, Experimental / Plant Genetics and Genomics / Polymorphism, Single Nucleotide / Probes / Prostate cancer / Protein Interaction Maps / Proteomics / Risk reduction / Sequence Analysis, DNA / Single nucleotide polymorphisms