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

BMC Genomics

Methodology Article

Christopher M Hovens¹  Niall M Corcoran¹  Matthew K H Hong¹  Zac Chatterton²  Nicholas C Wong³  Haroon Naeem⁴  Geoff Macintyre⁴  John S Pedersen⁵ 

[1] Australian Prostate Cancer Research Centre Epworth, Richmond, Australia and Division of Urology, Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Parkville, Australia;Cancer, Disease and Developmental Epigenetics, Murdoch Childrens Research Institute, Royal Children’s Hospital, Department of Paediatrics, The University of Melbourne, Melbourne, Australia;Cancer, Disease and Developmental Epigenetics, Murdoch Childrens Research Institute, Royal Children’s Hospital, Department of Paediatrics, The University of Melbourne, Melbourne, Australia;Ludwig Institute of Cancer Research, Olivia Newton John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, Australia;NICTA Victoria Research Laboratory, Department of Electrical and Electronic Engineering, The University of Melbourne, 3010, Parkville, Victoria, Australia;Department of Computing and Information Systems, Melbourne School of Engineering, The University of Melbourne, 3010, Melbourne, Victoria, Australia;TissuPath Specialist Pathology, Mount Waverley, 3149, Melbourne, Victoria, Australia;Faculty of Medicine, Nursing and Health Sciences, Monash University, 3800, Victoria, Australia;

关键词: HumanMethylation450K BeadChip;    SNPs;    INDELS;    Repetitive regions of DNA;    SNP arrays;    HM450K bead array;    Epigenome-wide association studies;    EWAS;    Cancer;    Epigenetics;   

DOI  :  10.1186/1471-2164-15-51

 received in 2013-06-29, accepted in 2014-01-15,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsWe 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.ConclusionsOur 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.

【 授权许可】

CC BY   
© Naeem et al.; licensee BioMed Central Ltd. 2014