Title
A comparative study of disease genes and drug targets in the human protein interactome.
Abstract
Disease genes cause or contribute genetically to the development of the most complex diseases. Drugs are the major approaches to treat the complex disease through interacting with their targets. Thus, drug targets are critical for treatment efficacy. However, the interrelationship between the disease genes and drug targets is not clear.In this study, we comprehensively compared the network properties of disease genes and drug targets for five major disease categories (cancer, cardiovascular disease, immune system disease, metabolic disease, and nervous system disease). We first collected disease genes from genome-wide association studies (GWAS) for five disease categories and collected their corresponding drugs based on drugs' Anatomical Therapeutic Chemical (ATC) classification. Then, we obtained the drug targets for these five different disease categories. We found that, though the intersections between disease genes and drug targets were small, disease genes were significantly enriched in targets compared to their enrichment in human protein-coding genes. We further compared network properties of the proteins encoded by disease genes and drug targets in human protein-protein interaction networks (interactome). The results showed that the drug targets tended to have higher degree, higher betweenness, and lower clustering coefficient in cancer Furthermore, we observed a clear fraction increase of disease proteins or drug targets in the near neighborhood compared with the randomized genes.The study presents the first comprehensive comparison of the disease genes and drug targets in the context of interactome. The results provide some foundational network characteristics for further designing computational strategies to predict novel drug targets and drug repurposing.
Year
DOI
Venue
2015
10.1186/1471-2105-16-S5-S1
BMC Bioinformatics
Keywords
Field
DocType
Drug Target, Disease Gene, Cluster Coefficient, Disease Category, Anatomical Therapeutic Chemical
Disease,Gene,Interactome,Biology,Genome-wide association study,Drug target,Regulation of gene expression,Computational biology,Bioinformatics,Genetics,Drug,DNA microarray
Journal
Volume
Issue
ISSN
16 Suppl 5
S-5
1471-2105
Citations 
PageRank 
References 
5
0.43
8
Authors
4
Name
Order
Citations
PageRank
Jingchun Sun150.43
Kevin Zhu250.43
W Zheng350.43
Hua Xu4773.27