Defense Date

2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biostatistics

First Advisor

Kellie Archer

Abstract

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 components 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. We present an extension of principal components analysis to quantify the existence of batch effects, called guided PCA (gPCA). We describe a test statistic that uses gPCA to test if 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. We further compare existing batch effect correction methods and apply gPCA to test their effectiveness. We conclude that our novel statistic that utilizes guided principal components analysis to identify whether batch effects exist in high-throughput genomic data is effective. Although our examples pertain to copy number data, gPCA is general and can be used on other data types as well.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2013

Included in

Biostatistics Commons

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