Evaluating and minimizing batch effects in metabolomics

Mass Spectrom Rev. 2022 May;41(3):421-442. doi: 10.1002/mas.21672. Epub 2020 Nov 25.


Determining metabolomic differences among samples of different phenotypes is a critical component of metabolomics research. With the rapid advances in analytical tools such as ultrahigh-resolution chromatography and mass spectrometry, an increasing number of metabolites can now be profiled with high quantification accuracy. The increased detectability and accuracy raise the level of stringiness required to reduce or control any experimental artifacts that can interfere with the measurement of phenotype-related metabolome changes. One of the artifacts is the batch effect that can be caused by multiple sources. In this review, we discuss the origins of batch effects, approaches to detect interbatch variations, and methods to correct unwanted data variability due to batch effects. We recognize that minimizing batch effects is currently an active research area, yet a very challenging task from both experimental and data processing perspectives. Thus, we try to be critical in describing the performance of a reported method with the hope of stimulating further studies for improving existing methods or developing new methods.

Keywords: NMR; batch effect; mass spectrometry; metabolome analysis; metabolomics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Mass Spectrometry
  • Metabolome*
  • Metabolomics* / methods