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
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Hepatitis-C Virus
Liver cirrhosis / cancer
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Genomic structure (Lindenbach et al., 2005) Viral genotypes (Simmonds et al., 2005)
4 SOC Drugs SVR Rates with SOC
5 RESPOND-2 (exp, phase III) REALIZE (exp, phase III)
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NS3 resistance mutations (Welsch et al, 2008) Interpretation and decision support (Roomp et al., 2006) Triple combination therapy
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Genotyping: Necessity of STAT-C (side effects) Resistance mutations: Identify resistance mutations known from literature Infer virus susceptibility Free, web-based genotype interpretation system: Provide MDs and virologists with information about an uploaded viral sequence
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9 Find nearest reference sub-genotype by sequence similarity
10 Summarize known resistance mutations by drug
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12 Identify known resistance patterns extracted from literature
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New Drugs
(Asselah et al., 2011)
Host genotype information
(Ge al., 2009)
Phenotypic Resistance Data
(Beerenwinkel et al., 2003)
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Sven-Eric Schelhorn Anna Marie Sikorski Michael Zeidler Saleta Sierra-Aragon Georg Friedrich Joachim Büch Rolf Kaiser Thomas Lengauer