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PLoS One. 2013 Oct 11;8(10):e76666. doi: 10.1371/journal.pone.0076666. eCollection 2013.

Multi-dimensional prioritization of dental caries candidate genes and its enriched dense network modules.

Author information

1
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.

Abstract

A number of genetic studies have suggested numerous susceptibility genes for dental caries over the past decade with few definite conclusions. The rapid accumulation of relevant information, along with the complex architecture of the disease, provides a challenging but also unique opportunity to review and integrate the heterogeneous data for follow-up validation and exploration. In this study, we collected and curated candidate genes from four major categories: association studies, linkage scans, gene expression analyses, and literature mining. Candidate genes were prioritized according to the magnitude of evidence related to dental caries. We then searched for dense modules enriched with the prioritized candidate genes through their protein-protein interactions (PPIs). We identified 23 modules comprising of 53 genes. Functional analyses of these 53 genes revealed three major clusters: cytokine network relevant genes, matrix metalloproteinases (MMPs) family, and transforming growth factor-beta (TGF-β) family, all of which have been previously implicated to play important roles in tooth development and carious lesions. Through our extensive data collection and an integrative application of gene prioritization and PPI network analyses, we built a dental caries-specific sub-network for the first time. Our study provided insights into the molecular mechanisms underlying dental caries. The framework we proposed in this work can be applied to other complex diseases.

PMID:
24146904
PMCID:
PMC3795720
DOI:
10.1371/journal.pone.0076666
[Indexed for MEDLINE]
Free PMC Article
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