Improved filtering of DNA methylation microarray data by detection p values and its impact on downstream analyses.

Affiliation

Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1057, New York, NY, 10029, USA. [Email]

Abstract

DNA methylation microarrays are popular for epigenome-wide association studies (EWAS), but spurious values complicate downstream analysis and threaten replication. Conventional cut-offs for detection p values for filtering out undetected probes were demonstrated in a single previous study as insufficient leading to many apparent methylation calls in samples from females in probes targeting the Y-chromosome. We present an alternative approach to calculate more accurate detection p values utilizing non-specific background fluorescence. We evaluate and compare our proposed approach of filtering observations with conventional ones by assessing the detection of Y-chromosome probes among males and females in 2755 samples from 17 studies on the 450K microarray and masking of large outliers between technical replicates and their impact downstream via an EWAS reanalysis.

Keywords

DNA methylation,Data cleaning,EWAS,Illumina 450K,Microarray analysis,Outlier detection,

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