Journal Article

Biomarker detection in the integration of multiple multi-class genomic studies

Shuya Lu, Jia Li, Chi Song, Kui Shen and George C. Tseng

in Bioinformatics

Volume 26, issue 3, pages 333-340
Published in print February 2010 | ISSN: 1367-4803
Published online December 2009 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btp669
Biomarker detection in the integration of multiple multi-class genomic studies

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Motivation: Systematic information integration of multiple-related microarray studies has become an important issue as the technology becomes mature and prevalent in the past decade. The aggregated information provides more robust and accurate biomarker detection. So far, published meta-analysis methods for this purpose mostly consider two-class comparison. Methods for combining multi-class studies and considering expression pattern concordance are rarely explored.

Results: In this article, we develop three integration methods for biomarker detection in multiple multi-class microarray studies: ANOVA-maxP, min-MCC and OW-min-MCC. We first consider a natural extension of combining P-values from the traditional ANOVA model. Since P-values from ANOVA do not guarantee to reflect the concordant expression pattern information across studies, we propose a multi-class correlation (MCC) measure to specifically seek for biomarkers of concordant inter-class patterns across a pair of studies. For both ANOVA and MCC approaches, we use extreme order statistics to identify biomarkers differentially expressed (DE) in all studies (i.e. ANOVA-maxP and min-MCC). The min-MCC method is further extended to identify biomarkers DE in partial studies by incorporating a recently developed optimally weighted (OW) technique (OW-min-MCC). All methods are evaluated by simulation studies and by three meta-analysis applications to multi-tissue mouse metabolism datasets, multi-condition mouse trauma datasets and multi-malignant-condition human prostate cancer datasets. The results show complementary strength of the three methods for different biological purposes.

Availability: http://www.biostat.pitt.edu/bioinfo/

Contact: ctseng@pitt.edu

Supplementary information: Supplementary data is available at Bioinformatics online.

Journal Article.  5844 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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