geno2pheno[hcv] Bastian Beggel and Sven-Eric Schelhorn May 2012 2 - PowerPoint PPT Presentation

geno2pheno[hcv] Bastian Beggel and Sven-Eric Schelhorn – May 2012

2 Hepatitis C Small, enveloped flavivirus (ss+ RNA) • 9.6 kb-long genome, 10 proteins • Affects hepatocytes in human, chimp • ~200 Million infected humans, most • of them not diagnosed Leads to liver cirrhosis, liver cancer • Hepatitis-C Virus Liver cirrhosis / cancer

3 Genomic structure of HCV Genomic structure Viral genotypes (Simmonds et al., 2005) (Lindenbach et al., 2005) - 6 genotypes - 30 subtypes

4 Standard of Care SOC Drugs SVR Rates with SOC

5 New Protease Inhibitors REALIZE (exp, phase III) RESPOND-2 (exp, phase III)

6 Resistance NS3 resistance mutations Triple combination therapy Interpretation and decision support (Welsch et al, 2008) (Roomp et al., 2006)

7 Geno2Pheno[hcv] Free, web-based genotype interpretation system: Provide MDs and virologists with information about an uploaded viral sequence Genotyping: Necessity of STAT-C (side effects ) Resistance mutations: Identify resistance mutations known from literature Infer virus susceptibility

www.genafor.org 8

9 Genotyping is based on NS5B Find nearest reference sub-genotype by sequence similarity

10 NS3: Resistance by drug Summarize known resistance mutations by drug

11 PDF Output

12 NS3 Alignment is presented Identify known resistance patterns extracted from literature

13 Outlook New Drugs Phenotypic Resistance Data Host genotype information (Asselah et al., 2011) (Beerenwinkel et al., 2003) (Ge al., 2009)

14 Acknowledgements Sven-Eric Schelhorn Anna Marie Sikorski Michael Zeidler Saleta Sierra-Aragon Georg Friedrich Joachim Büch Rolf Kaiser Thomas Lengauer