Identifying Co-targets to Fight Drug Resistance Based on a Random Walk Model

• Main Authors: Chen, Liang-Chun, 陳亮君
• Other Authors: Soo, Von-Wun
• Format: Others
• Language: en_US
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/43808110705043496498

碩士 === 國立清華大學 === 資訊系統與應用研究所 === 99 === Drug resistance has now posed more severe and emergent threats to human health and infectious disease treatment. However, the wet-lab approaches alone to counter drug resistance have so far still achieved limited success in understanding the underlying mechanisms and pathways of drug resistance. Our approach applied a heuristic search algorithm in order to extract drug response pathways from protein-protein interaction networks and used a random walk model to identify the potential co-target for effective antibacterial drugs. In this paper, we chose one of the killer infectious diseases, etiological organisms Mycobacterium tuberculosis (Mtb) as our test bed that was treated with Isoniazid (INH) and Ethionamide (ETA). We discovered that both of the genes in INH and ETA networks would facilitate survival related to triggering the processes in mycobactin synthesis, fatty acid synthesis/metabolism, and NADH-related processes. Efflux pumps appear to be the major mechanisms of resistance under INH and ETA drug treatment in Mtb. The results showed that the acetyl-CoA carboxylase is believed to be involved in fatty acid and mycolic acid biosynthesis and is strongly associated with the drug resistance mechanisms. Our analysis is consistent with the recent experimental findings and also found glycine-rich membrane, Adenosine triphosphate energy and cell wall-related processes to be potential co-targets for countering drug resistance. III keywords ： Drug resistance, A* search, Co-target, Random walk, Mycobacterium Tuberculosis