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V3 Loop Sequence Space Analysis Kasia Bo ek bozek@mpi-inf.mpg.de - - PowerPoint PPT Presentation
V3 Loop Sequence Space Analysis Kasia Bo ek bozek@mpi-inf.mpg.de - - PowerPoint PPT Presentation
V3 Loop Sequence Space Analysis Kasia Bo ek bozek@mpi-inf.mpg.de MPI Saarbrcken AREVIR meeting, Bonn 11.04.2008 V3 loop highly variable genome sequence related to coreceptor usage CCR5-CXCR4 coreceptor switch related to rapid disease
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Coreceptor prediction
in-silico phenotypic assays
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
V3 loop sequence space analysis
selection of sequences for experimental imaging of the HIV cell entry understanding of the distribution of V3 loop sequences in their sequence space
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Approach
2 datasets of sequences from Los Alamos NSI/ SI CCR5/ CXCR4/ R5X4 different distance measures Hamming distance BLOSUM matrix amino acid size and charge mutations on significant positions hierarchical clustering phylogenetical analysis using Splitstree
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
NSI vs. NSI SI vs. SI NSI vs. SI Distance distribution
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R5 vs. R5 X4 vs. X4 R5X4 vs. R5X4
Kasia Bożek AREVIR meeting Bonn 11.04.2008
Distance distribution
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Sequence clustering
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Sequence clustering
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Sequence clustering
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Sequence clustering
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
NSI R5 SI X4 R5X4
Sequence clustering
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis
evolution - not always is a branching tree-like process different phylogenetical signals in real data not always fitting into a unique tree Splitstree Splitstree – a tree-like network visualizing conflicting phylogenies
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
split
Phylogenetical analysis
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
SI NSI
Phylogenetical analysis
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Difficult sequences
unexpected placement of some sequences on the tree bad annotation? difficult cases?
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Difficult sequences
unexpected placement of some sequences on the tree bad annotation? difficult cases?
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Difficult sequences
unexpected placement of some sequences on the tree bad annotation? difficult cases?
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Difficult sequences
unexpected placement of some sequences on the tree bad annotation? difficult cases?
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Difficult sequences
unexpected placement of some sequences on the tree bad annotation? difficult cases?
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Difficult sequences
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
selection pressures on the R5 viruses high variability of X4 emergence of X4 and CD4+ T-cell count depletion cause or result of the disease progression?
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
immune system fail precedes the coreceptor switch coreceptor switch anticipates the disease 2 possible scenarios:
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
immune system fail precedes the coreceptor switch coreceptor switch anticipates the disease 2 possible scenarios:
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
immune system fail precedes the coreceptor switch coreceptor switch anticipates the disease highly mutated viruses only in cases of low CD4+ cell count 2 possible scenarios:
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
immune system fail precedes the coreceptor switch coreceptor switch anticipates the disease highly mutated viruses only in cases of low CD4+ cell count 2 possible scenarios:
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
immune system fail precedes the coreceptor switch coreceptor switch anticipates the disease highly mutated viruses only in cases of low CD4+ cell count mutated viruses within all levels of CD4+ cell count 2 possible scenarios:
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Disease and space position
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Kasia Bożek AREVIR meeting Bonn 11.04.2008
Conclusions
conservation of CCR5 V3 loop sequences highly variable CXCR4 viruses association to the immune escape scenario
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