Analyzing the Effects of Pretreatment Diversity on HCV Drug Treatment Responsiveness using Bayesian Partition methods
Yao Fu2, Gang Chen3, Xuan Guo4,Yi Pan4Jing Zhang1,2,3*
Affiliation
1Department of Mathematics and Statistics, Georgia State University
2Program of Computational Biology and Bioinformatics, Yale University
3Department of Statistics, Yale University
4Department of Computer Science, Georgia State University, Atlanta, Georgia, USA
Corresponding Author
Jing Zhang, Program of Computational Biology and Bioinformatics, Yale University, USA. E-mail: jzhang47@gsu.edu & Yi Pan, Department of Computer Science,Georgia State University, Atlanta,Georgia, USA. E-mail: yipan@gsu.edu
Citation
Zhang, J., et al. Analyzing the Effects of Pretreatment Diversity on HCV Drug Treatment Responsiveness Using Bayesian Partition methods. (2015) Bioinfo Proteom Img Anal 1(1): 1- 6.
Copy rights
© 2015 Zhang, J. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Abstract
Traditional therapies for Hepatitis C Virus (HCV) often yield unsatisfactory results. The reason for this may lie in the mechanism of drug resistance of the HCV virus. Despite doing a plain vanilla comparison between the treated and untreated groups, this paper takes a detour and investigates the drug resistance mechanism to interferon plus ribavirin combined therapy by comparing pretreatment sequence data between response and non-response patients in the NS5A region for genotype 1a HCV virus. We use Bayesian probabilistic models to detect single mutation or mutation combinations, and infer interaction structures between these mutations, to investigate the drug resistance combinations differences between those patients. We hope to decipher, at least partially, the reason behind the unsatisfactory results received from interferon plus ribavirin therapy.
Author Summary: HCV treatment results have been historically suboptimal[1-3]. HCV drug resistance, which further hinders the treatment effects, is caused by mutations of viral proteins that disrupt the drugs' binding but do not affect the viral survival. Due to the high rate and low fidelity of HCV replication, resistant strains quickly become dominant in a viral population under the selection pressure of a drug. M.J. Donlin et al indicate that pretreatment sequence diversity correlates with response effects[15]. We incorporate this idea and use a Bayesian approach to look into the pretreatment sequences diversity of HCV virus between response and non-response groups, under a combined treatment of interferon and ribavirin.