Title
Preserving biological heterogeneity with a permuted surrogate variable analysis for genomics batch correction.
Abstract
Motivation: Sample source, procurement process and other technical variations introduce batch effects into genomics data. Algorithms to remove these artifacts enhance differences between known biological covariates, but also carry potential concern of removing intragroup biological heterogeneity and thus any personalized genomic signatures. As a result, accurate identification of novel subtypes from batch-corrected genomics data is challenging using standard algorithms designed to remove batch effects for class comparison analyses. Nor can batch effects be corrected reliably in future applications of genomics-based clinical tests, in which the biological groups are by definition unknown a priori. Results: Therefore, we assess the extent to which various batch correction algorithms remove true biological heterogeneity. We also introduce an algorithm, permuted-SVA (pSVA), using a new statistical model that is blind to biological covariates to correct for technical artifacts while retaining biological heterogeneity in genomic data. This algorithm facilitated accurate subtype identification in head and neck cancer from gene expression data in both formalin-fixed and frozen samples. When applied to predict Human Papillomavirus (HPV) status, pSVA improved cross-study validation even if the sample batches were highly confounded with HPV status in the training set.
Year
DOI
Venue
2014
10.1093/bioinformatics/btu375
BIOINFORMATICS
Field
DocType
Volume
Clinical tests,Data mining,Standard algorithms,Covariate,Correction algorithm,Computer science,A priori and a posteriori,Genomics,Software,Statistical model,Bioinformatics
Journal
30
Issue
ISSN
Citations 
19
1367-4803
2
PageRank 
References 
Authors
0.46
3
8