Unsupervised gene set testing based on random matrix theory

BMC Bioinformatics

Methodology Article

H. Robert Frost¹  Christopher I. Amos¹ 

[1] Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, 03755, Hanover, NH, USA;

关键词: Gene set testing;    Pathway analysis;    Random matrix theory;    Tracy-Widom;    Marc̆enko-Pastur;   

DOI  :  10.1186/s12859-016-1299-8

 received in 2016-09-02, accepted in 2016-10-21,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundGene set testing, or pathway analysis, is a bioinformatics technique that performs statistical testing on biologically meaningful sets of genomic variables. Although originally developed for supervised analyses, i.e., to test the association between gene sets and an outcome variable, gene set testing also has important unsupervised applications, e.g., p-value weighting. For unsupervised testing, however, few effective gene set testing methods are available with support especially poor for several biologically relevant use cases.ResultsIn this paper, we describe two new unsupervised gene set testing methods based on random matrix theory, the Marc̆enko-Pastur Distribution Test (MPDT) and the Tracy-Widom Test (TWT), that support both self-contained and competitive null hypotheses. For the self-contained case, we contrast our proposed tests with the classic multivariate test based on a modified likelihood ratio criterion. For the competitive case, we compare the new tests against a competitive version of the classic test and our recently developed Spectral Gene Set Enrichment (SGSE) method. Evaluation of the TWT and MPDT methods is based on both simulation studies and a weighted p-value analysis of two real gene expression data sets using gene sets drawn from MSigDB collections.ConclusionsThe MPDT and TWT methods are novel and effective tools for unsupervised gene set analysis with superior statistical performance relative to existing techniques and the ability to generate biologically important results on real genomic data sets.

【 授权许可】

CC BY   
© The Author(s) 2016

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