Systems analysis of inflammatory bowel disease based on comprehensive gene information

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.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.Inflammatory Bowel Disease (IBD) is a chronic disease of unknown etiology that causes inflammation and ulcer in intestinal mucosa. Although IBD is still much less prevalent in Japan than in Western countries, the number of Japanese IBD patients has rapidly increased in the last 20 years [1]. This rising trend, also observed in the Asia-Pacific region [2,3] indicates that IBD is rapidly becoming a world-wide disease. There are two major sub-categories of IBD: Crohn's disease (CD) and ulcerative colitis (UC) [4]. Although the pathogenesis of IBD is not fully explained, genetic factors are suggested to contribute to dysregulation of intestinal immunity, leading to gastrointestinal injury.A genetic study of IBD was first reported in 1988 as an epidemiological study of CD patients [5]. Genome-wide scanning (GWS) studies have revealed nine IBD susceptibility loci (IBD1-9) [6] and one susceptibility gene (NOD2) [7]. Genome-Wide Association Studies (GWAS) and corresponding meta-analyses identified 71 susceptibility loci for CD [8] and 47 loci for UC [9]. Recently the genetic susceptibility to IBD was comprehensively reviewed in [10]. Another stud