Abstract
BackgroundThe 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 ResultsBased 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.ConclusionsThe 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.
Highlights
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
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 Inflammatory Bowel Disease (IBD) human disease network
There is clear categorization in drug indication to IBD according to the malignancy: aminosalicylate drugs for mild state patients, immunomodulator drugs and corticosteroid drugs for moderate state patients, and anti-TNF antibody drugs for severe state patients (Table 1)
Summary
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. Another study based on and analysis of molecular pathways suggested a significant overlap between IBD and autoimmune disorder, type 1 diabetes, ankylosing spondylitis (AS), multiple sclerosis, asthma [11], and rheumatoid arthritis (RA) [12]
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