HCV genotyping using statistical classification approach.
The genotype of Hepatitis C Virus (HCV) strains is an important determinant of the severity and aggressiveness of liver infection as well as patient response to antiviral therapy. Fast and accurate determination of viral genotype could provide direction in the clinical management of patients with chronic HCV infections. Using publicly available HCV nucleotide sequences, we built a global Position Weight Matrix (PWM) for the HCV genome. Based on the PWM, a set of genotype specific nucleotide sequence "signatures" were selected from the 5' NCR, CORE, E1, and NS5B regions of the HCV genome. We evaluated the predictive power of these signatures for predicting the most common HCV genotypes and subtypes. We observed that nucleotide sequence signatures selected from NS5B and E1 regions generally demonstrated stronger discriminant power in differentiating major HCV genotypes and subtypes than that from 5' NCR and CORE regions. Two discriminant methods were used to build predictive models. Through 10 fold cross validation, over 99% prediction accuracy was achieved using both support vector machine (SVM) and random forest based classification methods in a dataset of 1134 sequences for NS5B and 947 sequences for E1. Prediction accuracy for each genotype is also reported.
Qiu
Ping
P
Molecular Design and Informatics, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ping.qiu@spcorp.com
Cai
Xiao-Yan
XY
Ding
Wei
W
Zhang
Qing
Q
Norris
Ellie D
ED
Greene
Jonathan R
JR
D000465:Algorithms; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral; D005814:Genes, Viral; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D015203:Reproducibility of Results; D016415:Sequence Alignment; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase