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

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

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)1 - 15
Number of pages15
JournalBMC Genomics
Volume15
Issue number1 (Art. ID: 51)
DOIs
Publication statusPublished - 2014

Cite this

Naeem, Haroon ; Wong, Nicholas C ; Chatterton, Zac ; Hong, Matthew K H ; Pedersen, John S ; Corcoran, Niall M ; Hovens, Christopher M ; Macintyre, Geoff. / Reducing the risk of false discovery enabling identification of biologically significant genome-wide methylation status using the HumanMethylation450 array. In: BMC Genomics. 2014 ; Vol. 15, No. 1 (Art. ID: 51). pp. 1 - 15.
@article{a4e590c785f04772a900ea4539348d75,
title = "Reducing the risk of false discovery enabling identification of biologically significant genome-wide methylation status using the HumanMethylation450 array",
abstract = "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.",
author = "Haroon Naeem and Wong, {Nicholas C} and Zac Chatterton and Hong, {Matthew K H} and Pedersen, {John S} and Corcoran, {Niall M} and Hovens, {Christopher M} and Geoff Macintyre",
year = "2014",
doi = "10.1186/1471-2164-15-51",
language = "English",
volume = "15",
pages = "1 -- 15",
journal = "BMC Genomics",
issn = "1471-2164",
publisher = "BioMed Central",
number = "1 (Art. ID: 51)",

}

Reducing the risk of false discovery enabling identification of biologically significant genome-wide methylation status using the HumanMethylation450 array. / Naeem, Haroon; Wong, Nicholas C; Chatterton, Zac; Hong, Matthew K H; Pedersen, John S; Corcoran, Niall M; Hovens, Christopher M; Macintyre, Geoff.

In: BMC Genomics, Vol. 15, No. 1 (Art. ID: 51), 2014, p. 1 - 15.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Reducing the risk of false discovery enabling identification of biologically significant genome-wide methylation status using the HumanMethylation450 array

AU - Naeem, Haroon

AU - Wong, Nicholas C

AU - Chatterton, Zac

AU - Hong, Matthew K H

AU - Pedersen, John S

AU - Corcoran, Niall M

AU - Hovens, Christopher M

AU - Macintyre, Geoff

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - http://www.biomedcentral.com/content/pdf/1471-2164-15-51.pdf

U2 - 10.1186/1471-2164-15-51

DO - 10.1186/1471-2164-15-51

M3 - Article

VL - 15

SP - 1

EP - 15

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1 (Art. ID: 51)

ER -