The extraction of drug-disease correlations based on module distance in incomplete human interactome.
BACKGROUND
Extracting drug-disease correlations is crucial in unveiling disease mechanisms, as well as discovering new indications of available drugs, or drug repositioning. Both the interactome and the knowledge of disease-associated and drug-associated genes remain incomplete.


RESULTS
We present a new method to predict the associations between drugs and diseases. Our method is based on a module distance, which is originally proposed to calculate distances between modules in incomplete human interactome. We first map all the disease genes and drug genes to a combined protein interaction network. Then based on the module distance, we calculate the distances between drug gene sets and disease gene sets, and take the distances as the relationships of drug-disease pairs. We also filter possible false positive drug-disease correlations by p-value. Finally, we validate the top-100 drug-disease associations related to six drugs in the predicted results.


CONCLUSIONS
The overlapping between our predicted correlations with those reported in Comparative Toxicogenomics Database (CTD) and literatures, and their enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways demonstrate our approach can not only effectively identify new drug indications, but also provide new insight into drug-disease discovery.
School of Computer Science and Technology, Xidian University, Xi'an, 710071, People's Republic of China. lyu@xidian.edu.cn.
Liang
L
Yu
School of Computer Science and Technology, Xidian University, Xi'an, 710071, People's Republic of China.
Bingbo
B
Wang
School of Computer Science and Technology, Xidian University, Xi'an, 710071, People's Republic of China.
Xiaoke
X
Ma
School of Computer Science and Technology, Xidian University, Xi'an, 710071, People's Republic of China.
Lin
L
Gao
D019295:Computational Biology / Q000379:methods*; D004194:Disease / Q000235:genetics*; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D060066:Protein Interaction Maps
D004364:Pharmaceutical Preparations
Combined protein network; Drug-disease correlations; Incomplete human interactome; Module distance