Bioinformatics Advance Access published online on September 10, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm423
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Construction of a Reference Gene Association Networkf rom Multiple Profling Data: Application to Data Analysis
aComputer Science and Engineering, The Ohio State University, Columbus, OH43210
bApplied Genomics, Bristol-Myers Squibb Research and Development, Pennington, NJ 08534
*To whom correspondence should be addressed.Rui-Ru Ji, E-mail: Ruiru.Ji{at}bms.com
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Abstract |
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Motivation:Gene expression profiling is an important tool for gaining insight into biology. Novel strategies are required to analyze the growing archives of microarray data and extract useful information from them. One area of interest is in the construction of geneassociation networks from collections of profiling data. Various approaches have been proposed to construct gene networks using profiling data, and these networks have been used in functional inference as well as in data visualization. Here, we investigated a non-parametric approach to translate profiling data into a gene network. We explored the characteristics and utility of the resulting network and investigated the use of network information in analysis of variance models and hypothesis testing.
Results: Our work is composed of two parts: gene network construction and partitioning and hypothesis testing using sub-networks as groups. In the first part, multiple independently collected microarray datasets from the Gene Expression Omnibus data repository were analyzed to identify probe pairs that are positively co-regulated across the samples. A co-expression network was constructed based on a reciprocal ranking criteria and a false discovery rate analysis. We named this network Reference Gene Association (RGA) network. Then, the network was partitioned into densely connected sub-networks of probes using a multilevel graph partitioning algorithm. In the second part, we proposed a new, MANOVA-based approach that can take individual probe expression values as input and perform hypothesis testing at the sub-network level. We applied this MANOVA methodology to two published studies and our analysis indicated that the methodology is both effective and sensitive for identifying transcriptional sub-networks or pathways that are perturbed across treatments.
contact: Ruiru.Ji{at}bms.com, Nathan.Siemers{at}bms.com
Associate Editor: Prof. John Quackenbush
Received on January 31, 2007; revised on July 10, 2007; accepted on August 6, 2007
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