We present a Systems and a Network Medicine view of Crohn's Disease (CD) and Ulcerative Colitis (UC). We identify distinctly different genes and molecular processes involved in each disease , which are used to find potential drug targets, as well as novel candidate drugs. CD and UC , both under the umbrella of Inflammatory Bowel Diseases (IBD), involve many distinct molecular processes. The difference in  molecular processes is studied  using the different genes involved in each disease, and  explored further for drug targeting and drug repurposing. We have created a manually curated one-stop-shop informatics database (IBD-Omics) of genes , SNPs, drugs, biomarkers and microarray studies involved in CD and UC. This curated database was created by mining published literature , published studies such as the Genome Wide Association Studies, GWAS . The identified genes were then subject to informatics analytics software such as IPA, to reveal their molecular processes .A network pharmacology approach has identified newer targets and drugs that can be repurposed. We found that CD involved the Th1 pathway, while UC involved the Th2 pathway.Further analysis on gene networks demonstrated that dyslipidemia, epigenetic modulations and dysbiosis play a key role in CD, while inflammation, angiogenesis and potential carcinogenesis processes are involved in UC. Further, this dysbiosis and dyslipidemia in CD is associated with microbiome population change, suggestive of altered levels of micronutrients. Finally, using extended networks based on metabolomics and protein-protein interactions, we were able to suggest a role for synergistic approach in guiding treatment for CD and UC .
Introduction: Crohn's disease and ulcerative colitis , both under the umbrella of inflammatory bowel diseases (IBD), involve many distinct molecular processes. The difference in their molecular processes is studied by using the different genes involved in each disease, and it is explored further for drug targeting and drug repurposing. Methods: The initial set of genes was obtained by mining published literature and several curated databases . The identified genes were then subject to Systems and Network analysis to reveal their molecular processes and shed some light on their pathogenesis. Such methodologies have identified newer targets and drugs that can be repurposed. Results: We use a Systems and Network Medicine approach to understand the mechanism of actions of genes involved in IBD. From an initial set of genes mined from literature and curated databases, we used the Multi-Steiner Tree algorithm implemented within the CoVex systems medicine platform to expand each disease module by incorporating candidate genes with significant connections to the disease-related seed genes. Such expanded disease modules will identify a larger set of potential targets and drugs. We used the Closeness Centrality algorithm implemented within CoVex to search for newer targets and repurposable drugs. Through a network medicine approach, we provide a mechanistic view of the diseases and point to newer drugs and targets. Conclusion: We demonstrate that the Systems and Network Medicine approach is a powerful way to understand diseases and understand their mechanisms of action .
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We present a Systems and a Network Medicine view of
Introduction:
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Disease (CD) and Ulcerative Colitis (UC). We identify distinctly different genes and molecular processes involved in each disease , which are used to find potential drug targets, as well as novel candidate drugs. CD and UC
disease and ulcerative colitis
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Inflammatory Bowel Diseases
inflammatory bowel diseases
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We have created a manually curated one-stop-shop informatics database (IBD-Omics) of genes , SNPs, drugs, biomarkers and microarray studies involved in CD and UC. This curated database was created
Methods: The initial set of genes was obtained
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, published studies such as the Genome Wide Association Studies, GWAS
and several curated databases
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informatics analytics software such as IPA,
Systems and Network analysis
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.A network pharmacology approach has
and shed some light on their pathogenesis. Such methodologies have
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We found that CD involved the Th1 pathway, while UC involved the Th2 pathway.Further analysis on gene networks demonstrated that dyslipidemia, epigenetic modulations and dysbiosis play a key role in CD, while inflammation, angiogenesis and potential carcinogenesis processes are involved in UC. Further, this dysbiosis and dyslipidemia in CD is associated with microbiome population change, suggestive of altered levels of micronutrients. Finally, using extended networks based on metabolomics and protein-protein interactions, we were able to suggest a role for synergistic approach in guiding treatment for CD and UC
Results: We use a Systems and Network Medicine approach to understand the mechanism of actions of genes involved in IBD. From an initial set of genes mined from literature and curated databases, we used the Multi-Steiner Tree algorithm implemented within the CoVex systems medicine platform to expand each disease module by incorporating candidate genes with significant connections to the disease-related seed genes. Such expanded disease modules will identify a larger set of potential targets and drugs. We used the Closeness Centrality algorithm implemented within CoVex to search for newer targets and repurposable drugs. Through a network medicine approach, we provide a mechanistic view of the diseases and point to newer drugs and targets. Conclusion: We demonstrate that the Systems and Network Medicine approach is a powerful way to understand diseases and understand their mechanisms of action