Limits...
Systems analysis of inflammatory bowel disease based on comprehensive gene information.

Suzuki S, Takai-Igarashi T, Fukuoka Y, Wall DP, Tanaka H, Tonellato PJ - BMC Med. Genet. (2012)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

Show MeSH

Related in: MedlinePlus

The number of genes at each step of the analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3368714&req=5

Figure 1: The number of genes at each step of the analysis.

Mentions: Figure 1 shows the number of genes related to the two sibling diseases, IBDmild and IBDsevere. Genes for each sibling disease (1,264 for IBDmild and 869 for IBDsevere, Figure 1) were collected from the public databases: HugeNavigator, GeneCards, PharmGKB, and GAD. For each gene, g, we calculated the ranking score RFg by the frequency of the gene in databases and the frequency of the gene in PubMed according to equation (5). RFg was calculated for all genes associated with each sibling disease. We then determined a threshold score for each sibling disease used to exclude genes without significant evidence supporting their association with the sibling disease. To define the thresholds, we identified all genes in the two sibling disease gene sets which have verified association with IBD by direct literature review. We then scored all verified genes and chose the gene with lowest score in each sibling gene set (TNF for IBDmild and CRP for IBDsevere). Applying these thresholds to the RFg ranked list of sibling genes resulted in 250 and 253 genes for IBDmild and IBDsevere respectively. The intersection of the two sibling disease sets was 94 genes.


Systems analysis of inflammatory bowel disease based on comprehensive gene information.

Suzuki S, Takai-Igarashi T, Fukuoka Y, Wall DP, Tanaka H, Tonellato PJ - BMC Med. Genet. (2012)

The number of genes at each step of the analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368714&req=5

Figure 1: The number of genes at each step of the analysis.
Mentions: Figure 1 shows the number of genes related to the two sibling diseases, IBDmild and IBDsevere. Genes for each sibling disease (1,264 for IBDmild and 869 for IBDsevere, Figure 1) were collected from the public databases: HugeNavigator, GeneCards, PharmGKB, and GAD. For each gene, g, we calculated the ranking score RFg by the frequency of the gene in databases and the frequency of the gene in PubMed according to equation (5). RFg was calculated for all genes associated with each sibling disease. We then determined a threshold score for each sibling disease used to exclude genes without significant evidence supporting their association with the sibling disease. To define the thresholds, we identified all genes in the two sibling disease gene sets which have verified association with IBD by direct literature review. We then scored all verified genes and chose the gene with lowest score in each sibling gene set (TNF for IBDmild and CRP for IBDsevere). Applying these thresholds to the RFg ranked list of sibling genes resulted in 250 and 253 genes for IBDmild and IBDsevere respectively. The intersection of the two sibling disease sets was 94 genes.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

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.

Show MeSH
Related in: MedlinePlus