geno2pheno[hbv] - A Web Service for HBV Drug Resistance Analysis - PowerPoint PPT Presentation

geno2pheno[hbv] - A Web Service for HBV Drug Resistance Analysis Bastian Beggel Max-Planck-Institute for Informatics D-66123 Saarbrücken, Germany

geno2pheno[hbv] geno2pheno[hbv] • web-service for the analysis of HBV sequences • drug resistance: 3TC, ADF, LdT, ETV, TDF • escape mutations • rules based analysis • requires part of the RT domain (RT 80 - 252) Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] How to find the tool: http://www.genafor.org Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] Layout similar to geno2pheno[resistance] and geno2pheno[integrase] identifier upload files paste sequence align and predict Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] alignment sequence information drug resistance Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] – output options PDF CSV Bastian Beggel A Web Service for HBV Drug Resistance Analysis

The rule set summarizes available HBV literature HBV rule set (Jens Verheyen, Martin Däumer, Martin Obermeier; 07/2009) Drug Rule Definition Prediction TDF 194T possible resistant 173L resistant 180C or 180M resistant 204I or 204V or 204S resistant 3TC 181T resistant 191I resistant 80V or 80I possible resistant 181T or 181V resistant ADF 233V resistant 236T resistant (169T or 184A or 184G or 184I or 184S or 202G or 202I or resistant 250V) and (180C or 180M) and (204I or 204V) ETV 169T or 184A or 184G or 184I or 184S possible resistant 202G or 202I possible resistant 250V possible resistant 204I or 204V resistant LdT 80I or 80V possible resistant Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] – for the future The HOPE Project: • University Cologne Phenotypic Assay IC 50 values • Technical University of Munich • University Hospital Genome Leipzig • Medical School Hannover • University Bonn • University Giessen • University Essen • Max-Planck Institute Replication cycle for Informatics Transduction WT virus Cell culture Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – measurement Designed Sequences Blood samples Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – measurement selection database • Collection of HBV genotypes from multiple sources • Thanks to • Florian van Bömmel • Rolf Kaiser • Stefan Ross • Martin Stürmer • Benedikt Weissbrich • Karsten Wursthorn • 1492 HBV genotypes in our database (April 20 th , 2010) Database of diverse HBV genotypes Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – concepts of measurement selection TDF 3TC ADF ETV LdT Coverage of HBV ruleset Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – measurement selection process Selected Nr Mutations A B C D E G Total Measurements 1 180M,204V 88 8 2 36 1 8 143 6 2 204I 10 2 3 38 1 54 5 3 173L,180M,204V 30 14 4 48 3 4 180M,204I 12 1 14 27 3 5 181V 2 1 22 1 26 4 6 214A 1 20 2 23 3 7 236T 15 1 4 20 3 8 80I,204I 14 1 15 3 9 181V,236T 1 11 1 13 3 10 181T 6 5 1 12 3 11 180M,202G,204V 2 5 7 3 … … … … … … … … … … … … 44 202I,204I 1 1 1 Total 462 135 Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – measurement selection process TDF 3TC ADF ETV LdT Coverage of HBV ruleset Coverage of potential RAM Suggestions are welcome Suspicious cases from clinical data Bastian Beggel A Web Service for HBV Drug Resistance Analysis

Acknowledgements • Thomas Lengauer • Rolf Kaiser • Joachim Büch • Eugen Schülter • Andre Altmann • Jens Verheyen • Alex Thielen • Maria Fraune • HOPE Group • Martin Däumer • Martin Stürmer • Benedikt Weissbrich • U. Schuldenzucker Bastian Beggel A Web Service for HBV Drug Resistance Analysis

Thank You! Bastian Beggel A Web Service for HBV Drug Resistance Analysis