Identifying functional modules for coronary artery disease by a prior knowledge-based approach.
Until recently, the underlying genetic mechanisms for coronary artery disease (CAD) have been largely unknown, with just a list of genes identified accounting for very little of the disease in the population. Hence, a systematic dissection of the sophisticated interplays between these individual disease genes and their functional involvements becomes essential. Here, we presented a novel knowledge-based approach to identify the functional modules for CAD. First, we selected 266 disease genes in CADgene database as the initial seed genes, and used PPI knowledge as a guide to expand these genes into a CAD-specific gene network. Then, we used Newman's algorithm to decompose the primary network into 14 compact modules with high modularity. By analysis of these modules, we further identified 114 hub genes, all either directly or indirectly associated with CAD. Finally, by functional analysis of these modules, we revealed several novel pathogenic mechanisms for CAD (for examples, some yet rarely concerned like peptide YY receptor activity, Fc gamma R-mediated phagocytosis and actin cytoskeleton regulation etc.).
['Li|Haoli|H|', 'Zuo|Xiaoyu|X|', 'Ouyang|Ping|P|', 'Lin|Meihua|M|', 'Zhao|Zhong|Z|', 'Liang|Yan|Y|', 'Zhong|Shouqiang|S|', 'Rao|Shaoqi|S|']
D000465:Algorithms D003324:Coronary Artery Disease D030541:Databases, Genetic D053263:Gene Regulatory Networks D020022:Genetic Predisposition to Disease D006801:Humans D051188:Knowledge Bases D058977:Molecular Sequence Annotation
Coronary artery disease CAD PPI Data mining GO Gene Ontology Gene annotation Gene module HPRD Human Protein Reference Database Protein interaction maps Protein–protein interaction VSMC Vascular smooth muscle cell