An integrative analysis of gene expression and molecular interaction data to identify dys-regulated sub-networks in inflammatory bowel disease

BMC Bioinformatics

Research Article

Daniele Muraro¹  Alison Simmons¹ 

[1] Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, OX3 9DS Oxford, UK;

关键词: Inflammatory bowel disease;    Molecular interaction network;    Evolutionary algorithm;   

DOI  :  10.1186/s12859-016-0886-z

 received in 2015-06-22, accepted in 2016-01-08,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundInflammatory bowel disease (IBD) consists of two main disease-subtypes, Crohn’s disease (CD) and ulcerative colitis (UC); these subtypes share overlapping genetic and clinical features. Genome-wide microarray data enable unbiased documentation of alterations in gene expression that may be disease-specific. As genetic diseases are believed to be caused by genetic alterations affecting the function of signalling pathways, module-centric optimisation algorithms, whose aim is to identify sub-networks that are dys-regulated in disease, are emerging as promising approaches.ResultsIn order to account for the topological structure of molecular interaction networks, we developed an optimisation algorithm that integrates databases of known molecular interactions with gene expression data; such integration enables identification of differentially regulated network modules. We verified the performance of our algorithm by testing it on simulated networks; we then applied the same method to study experimental data derived from microarray analysis of CD and UC biopsies and human interactome databases. This analysis allowed the extraction of dys-regulated subnetworks under different experimental conditions (inflamed and uninflamed tissues in CD and UC). Optimisation was performed to highlight differentially expressed network modules that may be common or specific to the disease subtype.ConclusionsWe show that the selected subnetworks include genes and pathways of known relevance for IBD; in particular, the solutions found highlight cross-talk among enriched pathways, mainly the JAK/STAT signalling pathway and the EGF receptor signalling pathway. In addition, integration of gene expression with molecular interaction data highlights nodes that, although not being differentially expressed, interact with differentially expressed nodes and are part of pathways that are relevant to IBD. The method proposed here may help identifying dys-regulated sub-networks that are common in different diseases and sub-networks whose dys-regulation is specific to a particular disease.

【 授权许可】

CC BY   
© Muraro and Simmons. 2016

【 图 表 】

Fig. 2

12951_2015_155_Article_IEq47.gif

Fig. 4

Fig. 5