MetaDCN: Meta-analysis framework for differential co-expression network detection with an application in breast cancer

Li Zhu, Ying Ding, Cho Yi Chen, Lin Wang, Zhiguang Huo, Sunghwan Kim, Christos Sotiriou, Steffi Oesterreich, George C. Tseng*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Motivation: Gene co-expression network analysis from transcriptomic studies can elucidate gene-gene interactions and regulatory mechanisms. Differential co-expression analysis helps further detect alterations of regulatory activities in case/control comparison. Co-expression networks estimated from single transcriptomic study is often unstable and not generalizable due to cohort bias and limited sample size. With the rapid accumulation of publicly available transcriptomic studies, co-expression analysis combining multiple transcriptomic studies can provide more accurate and robust results. Results: In this paper, we propose a meta-analytic framework for detecting differentially co-expressed networks (MetaDCN). Differentially co-expressed seed modules are first detected by optimizing an energy function via simulated annealing. Basic modules sharing common pathways are merged into pathway-centric supermodules and a Cytoscape plug-in (MetaDCNExplorer) is developed to visualize and explore the findings. We applied MetaDCN to two breast cancer applications: ER+/ER- comparison using five training and three testing studies, and ILC/IDC comparison with two training and two testing studies. We identified 20 and 4 supermodules for ER+/ER- and ILC/IDC comparisons, respectively. Ranking atop are 'immune response pathway' and 'complement cascades pathway' for ER comparison, and 'extracellular matrix pathway' for ILC/IDC comparison. Without the need for prior information, the results from MetaDCN confirm existing as well as discover novel disease mechanisms in a systems manner.

Original languageEnglish
Pages (from-to)1121-1129
Number of pages9
JournalBioinformatics
Volume33
Issue number8
DOIs
StatePublished - 15 Apr 2017

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