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

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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 Saarbrcken, Germany geno2pheno[hbv] geno2pheno[hbv] web-service for the analysis of HBV sequences drug


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Bastian Beggel Max-Planck-Institute for Informatics D-66123 Saarbrücken, Germany

geno2pheno[hbv]

  • A Web Service for HBV Drug Resistance Analysis
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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv]

  • web-service for the analysis
  • f HBV sequences
  • drug resistance: 3TC,

ADF, LdT, ETV, TDF

  • escape mutations
  • rules based analysis
  • requires part of the RT

domain (RT 80 - 252)

geno2pheno[hbv]

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] How to find the tool: http://www.genafor.org

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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

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] drug resistance sequence information alignment

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] – output options PDF CSV

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HBV rule set (Jens Verheyen, Martin Däumer, Martin Obermeier; 07/2009)

Drug Rule Definition Prediction

TDF

194T possible resistant

3TC

173L resistant 180C or 180M resistant 204I or 204V or 204S resistant 181T resistant 191I resistant 80V or 80I possible resistant

ADF

181T or 181V resistant 233V resistant 236T resistant

ETV

(169T or 184A or 184G or 184I or 184S or 202G or 202I or 250V) and (180C or 180M) and (204I or 204V) resistant 169T or 184A or 184G or 184I or 184S possible resistant 202G or 202I possible resistant 250V possible resistant

LdT

204I or 204V resistant 80I or 80V possible resistant

The rule set summarizes available HBV literature

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

geno2pheno[hbv] – for the future IC 50 values

The HOPE Project:

  • University Cologne
  • Technical University
  • f Munich
  • University Hospital

Leipzig

  • Medical School

Hannover

  • University Bonn
  • University Giessen
  • University Essen
  • Max-Planck Institute

for Informatics

Genome WT virus Cell culture

Transduction

Replication cycle

Phenotypic Assay

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – measurement

Blood samples Designed Sequences

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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 20th, 2010)

Database of diverse HBV genotypes

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – concepts of measurement selection

Coverage of HBV ruleset

TDF 3TC ADF ETV LdT

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – measurement selection process

Nr Mutations A B C D E G Total Selected 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 … … … … … … … … … … … …

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

HOPE – measurement selection process

Coverage of HBV ruleset

TDF 3TC ADF ETV LdT

Coverage of potential RAM Suspicious cases from clinical data Suggestions are welcome

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Bastian Beggel A Web Service for HBV Drug Resistance Analysis

Acknowledgements

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

Thank You!