Gene prioritization in Type 2 Diabetes using domain interactions and network analysis.

BMC Genomics
Amitabh SharmaDwaipayan Bharadwaj

Abstract

Identification of disease genes for Type 2 Diabetes (T2D) by traditional methods has yielded limited success. Based on our previous observation that T2D may result from disturbed protein-protein interactions affected through disrupting modular domain interactions, here we have designed an approach to rank the candidates in the T2D linked genomic regions as plausible disease genes. Our approach integrates Weight value (Wv) method followed by prioritization using clustering coefficients derived from domain interaction network. Wv for each candidate is calculated based on the assumption that disease genes might be functionally related, mainly facilitated by interactions among domains of the interacting proteins. The benchmarking using a test dataset comprising of both known T2D genes and non-T2D genes revealed that Wv method had a sensitivity and specificity of 0.74 and 0.96 respectively with 9 fold enrichment. The candidate genes having a Wv > 0.5 were called High Weight Elements (HWEs). Further, we ranked HWEs by using the network property-the clustering coefficient (Ci). Each HWE with a Ci < 0.015 was prioritized as plausible disease candidates (HWEc) as previous studies indicate that disease genes tend to avoid dense clusterin...Continue Reading

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Citations

Aug 9, 2013·Current Diabetes Reports·Joachim Storling, Caroline Anna Brorsson
Jun 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lukas Adrian BerchtoldJoachim Størling
May 23, 2013·Omics : a Journal of Integrative Biology·Vinay RandhawaGanesh Bagler
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Oct 4, 2013·Science Translational Medicine·Xiaochen SunNicholas P Tatonetti
Oct 16, 2015·PLoS Computational Biology·Marinka ŽitnikBlaž Zupan
Apr 30, 2019·Frontiers in Genetics·Abhijeet R SonawaneAmitabh Sharma

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Methods Mentioned

BETA
two-hybrid

Software Mentioned

SUSPECTS
GeneWays
BiNGO
Ensembl
Biological Networks Gene Ontology tool ( BiNGO )
Cytoscape
mdraw
NetworkAnalyzer
Protfun
InterDom

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