A new statistic for identifying batch effects in high-throughput genomic data that uses guided principal component analysis

Sarah E. Reese, Kellie J. Archer, Terry M. Therneau, Elizabeth J. Atkinson, Celine M. Vachon, Mariza De Andrade, Jean Pierre A. Kocher, Jeanette E. Eckel-Passow

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Motivation: Batch effects are due to probe-specific systematic variation between groups of samples (batches) resulting from experimental features that are not of biological interest. Principal component analysis (PCA) is commonly used as a visual tool to determine whether batch effects exist after applying a global normalization method. However, PCA yields linear combinations of the variables that contribute maximum variance and thus will not necessarily detect batch effects if they are not the largest source of variability in the data. Results: We present an extension of PCA to quantify the existence of batch effects, called guided PCA (gPCA). We describe a test statistic that uses gPCA to test whether a batch effect exists. We apply our proposed test statistic derived using gPCA to simulated data and to two copy number variation case studies: the first study consisted of 614 samples from a breast cancer family study using Illumina Human 660 bead-chip arrays, whereas the second case study consisted of 703 samples from a family blood pressure study that used Affymetrix SNP Array 6.0. We demonstrate that our statistic has good statistical properties and is able to identify significant batch effects in two copy number variation case studies. Conclusion: We developed a new statistic that uses gPCA to identify whether batch effects exist in high-throughput genomic data. Although our examples pertain to copy number data, gPCA is general and can be used on other data types as well.

Original languageEnglish (US)
Pages (from-to)2877-2883
Number of pages7
JournalBioinformatics
Volume29
Issue number22
DOIs
StatePublished - Nov 15 2013

ASJC Scopus subject areas

  • Statistics and Probability
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Computational Theory and Mathematics
  • Computational Mathematics

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