Research On Drug Relocation Based On Network Model

The pathogenesis of complex diseases has been one of the major problems in the field of human health,the traditional method of drug development costs a lot of time and money,has been unable to meet people’s needs.Finding new uses for existing drugs(drug repositioning)has become a new strategy for decades to treat more patients.Few traditional approaches consider the tissue specificities of diseases.Moreover,disease genes,drug targets and protein interaction(PPI)networks remain largely incomplete.Therefore,computational approaches based on the network model and integrating the different biological data to drug repositioning has received more and more attention.The thesis is mainly composed of the following three parts:(1)The effect of drug repositioning based on different tissue-specific networks.(2)Based on tissue specificities of diseases,we apply the triangularly balanced theory and the module distance defined for incomplete interaction networks to build drug-disease associations.Our method is named as TTMD(Tissue specificity,Triangle balance theory and Module Distance).Firstly,we combine three different drug similarity networks.Then,in the tissue-specific PPI network of a disease,we calculate its similarities with drugs using module distance.Finally,breast cancer and hepatocellular carcinoma(HCC)are taken as case studies.CTD database,Clinical verification,literature mining and KEGG pathways enrichment analysis are further conducted for the predicted associations.(3)We have integrated mi RNA data to drug repositioning research,breast cancer is taken as case study,we use mi RNA as a bridge to predict the relationship between drugs and disease.CTD database,literature excavation and Clinical verification indicating that it is feasible to conduct drug repositioning with mi RNA data.Through the study,we found that drug predictions based on disease related tissue-specific networks can improve the accuracy of the results.Our method TTMD is an effective approach for predicting new drug indications for tissue-specific diseases and provides potential values for the treatments of complex diseases.The use of mi RNA data for drug repositioning can help us understanding the pathogenesis of complex diseases.