NDLI: A Microarray Platform-Independent Classification Tool for Cell of Origin Class Allows Comparative Analysis of Gene Expression in Diffuse Large B-cell Lymphoma

Content Provider	PubMed Central
Author	Care, Matthew A. Sharon, Barrans Lisa, Worrillow Jack, Andrew Westhead, David R. Tooze, Reuben M.
Editor	Richards, Kristy L.
Copyright Year	2013
Abstract	Cell of origin classification of diffuse large B-cell lymphoma (DLBCL) identifies subsets with biological and clinical significance. Despite the established nature of the classification existing studies display variability in classifier implementation, and a comparative analysis across multiple data sets is lacking. Here we describe the validation of a cell of origin classifier for DLBCL, based on balanced voting between 4 machine-learning tools: the DLBCL automatic classifier (DAC). This shows superior survival separation for assigned Activated B-cell (ABC) and Germinal Center B-cell (GCB) DLBCL classes relative to a range of other classifiers. DAC is effective on data derived from multiple microarray platforms and formalin fixed paraffin embedded samples and is parsimonious, using 20 classifier genes. We use DAC to perform a comparative analysis of gene expression in 10 data sets (2030 cases). We generate ranked meta-profiles of genes showing consistent class-association using ≥6 data sets as a cut-off: ABC (414 genes) and GCB (415 genes). The transcription factor ZBTB32 emerges as the most consistent and differentially expressed gene in ABC-DLBCL while other transcription factors such as ARID3A, BATF, and TCF4 are also amongst the 24 genes associated with this class in all datasets. Analysis of enrichment of 12323 gene signatures against meta-profiles and all data sets individually confirms consistent associations with signatures of molecular pathways, chromosomal cytobands, and transcription factor binding sites. We provide DAC as an open access Windows application, and the accompanying meta-analyses as a resource.
Related Links	http://dx.doi.org/10.1371/journal.pone.0055895
Starting Page	55895
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	2
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-02-12
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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