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This article is part of the supplement: Tenth International Conference on Bioinformatics. First ISCB Asia Joint Conference 2011 (InCoB/ISCB-Asia 2011): Bioinformatics

Open Access Proceedings

Finding consistent disease subnetworks across microarray datasets

Donny Soh123*, Difeng Dong1, Yike Guo2 and Limsoon Wong1

Author Affiliations

1 National University of Singapore, 13 Computing Drive, Singapore 117417

2 Imperial College London, 180 Queens Gate, London SW7 2BZ, UK

3 Institute for Infocomm Research, 1 Fusionopolis Way, 21-01 Connexis (South Tower), Singapore 138632

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BMC Bioinformatics 2011, 12(Suppl 13):S15  doi:10.1186/1471-2105-12-S13-S15

Published: 30 November 2011

Abstract

Background

While contemporary methods of microarray analysis are excellent tools for studying individual microarray datasets, they have a tendency to produce different results from different datasets of the same disease. We aim to solve this reproducibility problem by introducing a technique (SNet). SNet provides both quantitative and descriptive analysis of microarray datasets by identifying specific connected portions of pathways that are significant. We term such portions within pathways as “subnetworks”.

Results

We tested SNet on independent datasets of several diseases, including childhood ALL, DMD and lung cancer. For each of these diseases, we obtained two independent microarray datasets produced by distinct labs on distinct platforms. In each case, our technique consistently produced almost the same list of significant nontrivial subnetworks from two independent sets of microarray data. The gene-level agreement of these significant subnetworks was between 51.18% to 93.01%. In contrast, when the same pairs of microarray datasets were analysed using GSEA, t-test and SAM, this percentage fell between 2.38% to 28.90% for GSEA, 49.60% tp 73.01% for t-test, and 49.96% to 81.25% for SAM. Furthermore, the genes selected using these existing methods did not form subnetworks of substantial size. Thus it is more probable that the subnetworks selected by our technique can provide the researcher with more descriptive information on the portions of the pathway actually affected by the disease.

Conclusions

These results clearly demonstrate that our technique generates significant subnetworks and genes that are more consistent and reproducible across datasets compared to the other popular methods available (GSEA, t-test and SAM). The large size of subnetworks which we generate indicates that they are generally more biologically significant (less likely to be spurious). In addition, we have chosen two sample subnetworks and validated them with references from biological literature. This shows that our algorithm is capable of generating descriptive biologically conclusions.