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Citation
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HERO ID
1579252
Reference Type
Journal Article
Title
Batch effects and pathway analysis: Two potential perils in cancer studies involving DNA methylation array analysis
Author(s)
Harper, KN; Peters, BA; Gamble, MV
Year
2013
Is Peer Reviewed?
Yes
Journal
Cancer Epidemiology Biomarkers and Prevention
ISSN:
1055-9965
EISSN:
1538-7755
Volume
22
Issue
6
Page Numbers
1052-1060
Language
English
PMID
23629520
DOI
10.1158/1055-9965.EPI-13-0114
Web of Science Id
WOS:000320643200007
URL
http://cebp.aacrjournals.org/lookup/doi/10.1158/1055-9965.EPI-13-0114
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Abstract
Background: DNA methylation microarrays have become an increasingly popular means of studying the role of epigenetics in cancer, though the methods used to analyze these arrays are still being developed and existing methods are not always widely disseminated among microarray users.
Methods: We investigated two problems likely to confront DNA methylation microarray users: 1) batch effects; and 2) the use of widely available pathway analysis software to analyze results. First, DNA taken from individuals exposed to low and high levels of drinking water arsenic were plated twice on Illumina's Infinium 450K humanmethylation array, once in order of exposure and again following randomization. Second, we performed simulations in which random CpG sites were drawn from the 450K array and subjected to pathway analysis using Ingenuity's IPA software.
Results: The majority of differentially methylated CpG sites identified in Run One were due to batch effects; few sites were also identified in Run Two. In addition, the pathway analysis software reported many significant associations between our data, randomly drawn from the 450K array, and various diseases and biological functions.
Conclusions: Data from our own laboratory illustrate the pitfalls of not properly controlling for chip-specific batch effects as well as using pathway analysis software created for gene expression arrays to analyze DNA methylation array data.
Impact: We present evidence that 1) chip-specific effects can simulate plausible differential methylation results; and 2) popular pathway analysis software developed for expression arrays can yield spurious results when used in tandem with methylation microarrays.
Tags
•
Arsenic Hazard ID
PubMed
Considered New
PubMed
Considered New
PubMed
Considered New
WOS
Considered New
WOS
Considered New
2. Lit Search Updates through Oct 2015
PubMed
WOS
Considered
7. Other Studies through Oct 2015
Non-Arsenic
•
Arsenic (Inorganic)
1. Literature
Lit search updates through Oct 2015
3. Hazard ID Screening
Other potentially supporting studies
5. Susceptibility Screening
Excluded/Not relevant
•
Arsenic Susceptibility
1. Susceptibility Literature Screening
Keyword Search
2. Excluded
Not Relevant
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