Exploring Drug Treatment Patterns Based on the Action of Drug and Multilayer Network Model.

Liping Zheng,Lin Gao,Liang Yu,Shuhang Wang,Quan Zou,Yayong Shi

doi:10.3390/ijms21145014

Abstract

Some drugs can be used to treat multiple diseases, suggesting potential patterns in drug treatment. Determination of drug treatment patterns can improve our understanding of the mechanisms of drug action, enabling drug repurposing. A drug can be associated with a multilayer tissue-specific protein–protein interaction (TSPPI) network for the diseases it is used to treat. Proteins usually interact with other proteins to achieve functions that cause diseases. Hence, studying drug treatment patterns is similar to studying common module structures in multilayer TSPPI networks. Therefore, we propose a network-based model to study the treatment patterns of drugs. The method was designated SDTP (studying drug treatment pattern) and was based on drug effects and a multilayer network model. To demonstrate the application of the SDTP method, we focused on analysis of trichostatin A (TSA) in leukemia, breast cancer, and prostate cancer. We constructed a TSPPI multilayer network and obtained candidate drug-target modules from the network. Gene ontology analysis provided insights into the significance of the drug-target modules and co-expression networks. Finally, two modules were obtained as potential treatment patterns for TSA. Through analysis of the significance, composition, and functions of the selected drug-target modules, we validated the feasibility and rationality of our proposed SDTP method for identifying drug treatment patterns. In summary, our novel approach used a multilayer network model to overcome the shortcomings of single-layer networks and combined the network with information on drug activity. Based on the discovered drug treatment patterns, we can predict the potential diseases that the drug can treat. That is, if a disease-related protein module has a similar structure, then the drug is likely to be a potential drug for the treatment of the disease.

Highlights

Drugs interact with target and non-target molecules, triggering downstream signal cascades and disrupting the cell’s transcriptome [1]
Discovering new drug targets is critical for improving our understanding of the mechanisms of drug action [2], which is essential for drug discovery [3,4,5,6], clinical trials, and overcoming drug resistance [7,8]
The p values were all less than 0.05. These findings indicated the importance of M17 and M18 in these tissue-specific protein–protein interaction (TSPPI) networks, suggesting that trichostatin A (TSA) may be used to treat other diseases by acting on M17 and M18

Summary

Introduction

Drugs interact with target and non-target molecules, triggering downstream signal cascades and disrupting the cell’s transcriptome [1]. The mechanisms mediating the effects of drugs on targets have been widely studied [9,10,11,12,13,14,15]. Drug targets are limited to a single gene and can include modules or pathways that participate in the regulation of disease processes [16]. Each gene in the drug-target module may not be helpful for disease treatment, combinations of the genes within the module may play important roles in disease treatment [16]. By targeting multiple genes in the drug-target module, it may be possible to identify the function of genes related to complex disease pathology at the tissue level [17,18]

Methods

Results

Conclusion