Open Access Research article

Systems analysis of inflammatory bowel disease based on comprehensive gene information

Satoru Suzuki1, Takako Takai-Igarashi2*, Yutaka Fukuoka2, Dennis P Wall3, Hiroshi Tanaka2 and Peter J Tonellato3

Author Affiliations

1 Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan

2 Graduate School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan

3 Center for Biomedical Informatics, Harvard Medical School, 10 Shattuck Street, Boston, MA 02115, USA

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BMC Medical Genetics 2012, 13:25  doi:10.1186/1471-2350-13-25

Published: 5 April 2012

Abstract

Background

The rise of systems biology and availability of highly curated gene and molecular information resources has promoted a comprehensive approach to study disease as the cumulative deleterious function of a collection of individual genes and networks of molecules acting in concert. These "human disease networks" (HDN) have revealed novel candidate genes and pharmaceutical targets for many diseases and identified fundamental HDN features conserved across diseases. A network-based analysis is particularly vital for a study on polygenic diseases where many interactions between molecules should be simultaneously examined and elucidated. We employ a new knowledge driven HDN gene and molecular database systems approach to analyze Inflammatory Bowel Disease (IBD), whose pathogenesis remains largely unknown.

Methods and Results

Based on drug indications for IBD, we determined sibling diseases of mild and severe states of IBD. Approximately 1,000 genes associated with the sibling diseases were retrieved from four databases. After ranking the genes by the frequency of records in the databases, we obtained 250 and 253 genes highly associated with the mild and severe IBD states, respectively. We then calculated functional similarities of these genes with known drug targets and examined and presented their interactions as PPI networks.

Conclusions

The results demonstrate that this knowledge-based systems approach, predicated on functionally similar genes important to sibling diseases is an effective method to identify important components of the IBD human disease network. Our approach elucidates a previously unknown biological distinction between mild and severe IBD states.

Keywords:
Inflammatory bowel disease (IBD); Disease related genes; Protein-protein interaction networks; GO based functional score; Interpretation of pathogenesis