Universität zu Köln

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 ORCID: 0000-0003-3801-2640 (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:	Creators Email ORCID ORCID Put Code Kalaghatgi, Prabhav UNSPECIFIED UNSPECIFIED UNSPECIFIED Sikorski, Anna Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Knops, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Rupp, Daniel UNSPECIFIED UNSPECIFIED UNSPECIFIED Sierra, Saleta UNSPECIFIED UNSPECIFIED UNSPECIFIED Heger, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Neumann-Fraune, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Beggel, Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Walker, Andreas UNSPECIFIED orcid.org/0000-0002-8736-0863 UNSPECIFIED Timm, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Hauke UNSPECIFIED UNSPECIFIED UNSPECIFIED Obermeier, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartenschlager, Ralf UNSPECIFIED orcid.org/0000-0001-5601-9307 UNSPECIFIED Lengauer, Thomas UNSPECIFIED orcid.org/0000-0003-3801-2640 UNSPECIFIED
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:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Mathematics and Computer Science > Institute of Computer Science
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language IN-VITRO RESISTANCE; SERINE-PROTEASE INHIBITORS; DAILY SIMEPREVIR TMC435; VIRUS GENOTYPE 1B; DRUG-RESISTANCE; NS5A INHIBITOR; VIROLOGICAL RESPONSE; NULL RESPONDERS; NAIVE PATIENTS; MUTATION-RATE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27560