Kalaghatgi, Prabhav, Sikorski, Anna Maria, Knops, Elena, Rupp, Daniel, Sierra, Saleta, Heger, Eva, Neumann-Fraune, Maria, Beggel, Bastian, Walker, Andreas ORCID: 0000-0002-8736-0863, Timm, Joerg, Walter, Hauke, Obermeier, Martin, Kaiser, Rolf, Bartenschlager, Ralf ORCID: 0000-0001-5601-9307 and Lengauer, Thomas (2016). Geno2pheno([HCV]) - A Web-based Interpretation System to Support Hepatitis C Treatment Decisions in the Era of Direct-Acting Antiviral Agents. PLoS One, 11 (5). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

The face of hepatitis C virus (HCV) therapy is changing dramatically. Direct-acting antiviral agents (DAAs) specifically targeting HCV proteins have been developed and entered clinical practice in 2011. However, despite high sustained viral response (SVR) rates of more than 90%, a fraction of patients do not eliminate the virus and in these cases treatment failure has been associated with the selection of drug resistance mutations (RAMs). RAMs may be prevalent prior to the start of treatment, or can be selected under therapy, and furthermore they can persist after cessation of treatment. Additionally, certain DAAs have been approved only for distinct HCV genotypes and may even have subtype specificity. Thus, sequence analysis before start of therapy is instrumental for managing DAA-based treatment strategies. We have created the interpretation system geno2pheno([HCV]) (g2p([HCV])) to analyse HCV sequence data with respect to viral subtype and to predict drug resistance. Extensive reviewing and weighting of literature related to HCV drug resistance was performed to create a comprehensive list of drug resistance rules for inhibitors of the HCV protease in non-structural protein 3 (NS3-protease: Boceprevir, Paritaprevir, Simeprevir, Asunaprevir, Grazoprevir and Telaprevir), the NS5A replicase factor (Daclatasvir, Ledipasvir, Elbasvir and Ombitasvir), and the NS5B RNA-dependent RNA polymerase (Dasabuvir and Sofosbuvir). Upon submission of up to eight sequences, g2p([HCV]) aligns the input sequences, identifies the genomic region(s), predicts the HCV geno- and subtypes, and generates for each DAA a drug resistance prediction report. g2p([HCV]) offers easy-to-use and fast subtype and resistance analysis of HCV sequences, is continuously updated and freely accessible under http://hcv.geno2pheno.org/index.php. The system was partially validated with respect to the NS3-protease inhibitors Boceprevir, Telaprevir and Simeprevir by using data generated with recombinant, phenotypic cell culture assays obtained from patients' virus variants.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kalaghatgi, PrabhavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sikorski, Anna MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knops, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rupp, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sierra, SaletaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heger, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumann-Fraune, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beggel, BastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walker, AndreasUNSPECIFIEDorcid.org/0000-0002-8736-0863UNSPECIFIED
Timm, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walter, HaukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Obermeier, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenschlager, RalfUNSPECIFIEDorcid.org/0000-0001-5601-9307UNSPECIFIED
Lengauer, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-275609
DOI: 10.1371/journal.pone.0155869
Journal or Publication Title: PLoS One
Volume: 11
Number: 5
Date: 2016
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1932-6203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IN-VITRO RESISTANCE; SERINE-PROTEASE INHIBITORS; DAILY SIMEPREVIR TMC435; VIRUS GENOTYPE 1B; DRUG-RESISTANCE; NS5A INHIBITOR; VIROLOGICAL RESPONSE; NULL RESPONDERS; NAIVE PATIENTS; MUTATION-RATEMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27560

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