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Simulating ComBat: how batch correction can lead to the systematic introduction of false positive results in DNA methylation microarray studies.


ABSTRACT:

Background

Systematic technical effects-also called batch effects-are a considerable challenge when analyzing DNA methylation (DNAm) microarray data, because they can lead to false results when confounded with the variable of interest. Methods to correct these batch effects are error-prone, as previous findings have shown.

Results

Here, we demonstrate how using the R function ComBat to correct simulated Infinium HumanMethylation450 BeadChip (450 K) and Infinium MethylationEPIC BeadChip Kit (EPIC) DNAm data can lead to a large number of false positive results under certain conditions. We further provide a detailed assessment of the consequences for the highly relevant problem of p-value inflation with subsequent false positive findings after application of the frequently used

SUBMITTER: Zindler T 

PROVIDER: S-EPMC7328269 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature