Dataset Information

Multivariate search for differentially expressed gene combinations.

ABSTRACT:

Background

To identify differentially expressed genes, it is standard practice to test a two-sample hypothesis for each gene with a proper adjustment for multiple testing. Such tests are essentially univariate and disregard the multidimensional structure of microarray data. A more general two-sample hypothesis is formulated in terms of the joint distribution of any sub-vector of expression signals.

Results

By building on an earlier proposed multivariate test statistic, we propose a new algorithm for identifying differentially expressed gene combinations. The algorithm includes an improved random search procedure designed to generate candidate gene combinations of a given size. Cross-validation is used to provide replication stability of the search procedure. A permutation two-sample test is used for significance testing. We design a multiple testing procedure to control the family-wise error rate (FWER) when selecting significant combinations of genes that result from a successive selection procedure. A target set of genes is composed of all significant combinations selected via random search.

Conclusions

A new algorithm has been developed to identify differentially expressed gene combinations. The performance of the proposed search-and-testing procedure has been evaluated by computer simulations and analysis of replicated Affymetrix gene array data on age-related changes in gene expression in the inner ear of CBA mice.

SUBMITTER: Xiao Y

PROVIDER: S-EPMC529250 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature

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Publications

Multivariate search for differentially expressed gene combinations.

Xiao Yuanhui Y Frisina Robert R Gordon Alexander A Klebanov Lev L Yakovlev Andrei A

BMC bioinformatics 20041026

<h4>Background</h4>To identify differentially expressed genes, it is standard practice to test a two-sample hypothesis for each gene with a proper adjustment for multiple testing. Such tests are essentially univariate and disregard the multidimensional structure of microarray data. A more general two-sample hypothesis is formulated in terms of the joint distribution of any sub-vector of expression signals.<h4>Results</h4>By building on an earlier proposed multivariate test statistic, we propose ...[more]

PMID: 15507138

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Project description:BACKGROUND:Researches have been conducted for the identification of differentially expressed genes (DEGs) by generating and mining of cDNA expressed sequence tags (ESTs) for more than a decade. Although the availability of public databases make possible the comprehensive mining of DEGs among the ESTs from multiple tissue types, existing studies usually employed statistics suitable only for two categories. Multi-class test has been developed to enable the finding of tissue specific genes, but subsequent search for cancer genes involves separate two-category test only on the ESTs of the tissue of interest. This constricts the amount of data used. On the other hand, simple pooling of cancer and normal genes from multiple tissue types runs the risk of Simpson's paradox. Here we presented a different approach which searched for multi-cancer DEG candidates by analyzing all pertinent ESTs in all categories and narrowing down the cancer biomarker candidates via integrative analysis with microarray data and selection of secretory and membrane protein genes as well as incorporation of network analysis. Finally, the differential expression patterns of three selected cancer biomarker candidates were confirmed by real-time qPCR analysis. RESULTS:Seven hundred and twenty three primary DEG candidates (p-value < 0.05 and lower bound of confidence interval of odds ratio ? 1.65) were selected from a curated EST database with the application of Cochran-Mantel-Haenszel statistic (CMH). GeneGO analysis results indicated this set as neoplasm enriched. Cross-examination with microarray data further narrowed the list down to 235 genes, among which 96 had membrane or secretory annotations. After examined the candidates in protein interaction network, public tissue expression databases, and literatures, we selected three genes for further evaluation by real-time qPCR with eight major normal and cancer tissues. The higher-than-normal tissue expression of COL3A1, DLG3, and RNF43 in some of the cancer tissues is in agreement with our in silico predictions. CONCLUSIONS:Searching digitized transcriptome using CMH enabled us to identify multi-cancer differentially expressed gene candidates. Our methodology demonstrated simultaneously analysis for cancer biomarkers of multiple tissue types with the EST data. With the revived interest in digitizing the transcriptomes by NGS, cancer biomarkers could be more precisely detected from the ESTs. The three candidates identified in this study, COL3A1, DLG3, and RNF43, are valuable targets for further evaluation with a larger sample size of normal and cancer tissue or serum samples.

Dataset Information

Multivariate search for differentially expressed gene combinations.

Background

Results

Conclusions

Publications

Multivariate search for differentially expressed gene combinations.

Similar Datasets

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