V3 Loop Sequence Space Analysis Kasia Bo ż ek bozek@mpi-inf.mpg.de MPI Saarbrücken AREVIR meeting, Bonn 11.04.2008
V3 loop highly variable genome sequence related to coreceptor usage CCR5-CXCR4 coreceptor switch related to rapid disease progression importance of coreceptor prediction Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Coreceptor prediction in-silico phenotypic assays Kasia Bo ż ek 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 Kasia Bo ż ek 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 Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
NSI vs. NSI Distance distribution SI vs. SI NSI vs. SI Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
R5 vs. R5 Distance distribution X4 vs. X4 R5X4 vs. R5X4 Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Sequence clustering NSI R5 R5X4 SI X4 Kasia Bo ż ek 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 – a tree-like network visualizing conflicting phylogenies Splitstree Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis split Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis SI NSI Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Phylogenetical analysis Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Difficult sequences Kasia Bo ż ek 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? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Disease and space position 2 possible scenarios: immune system fail precedes the coreceptor switch coreceptor switch anticipates the disease Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Disease and space position 2 possible scenarios: immune system fail precedes the coreceptor switch coreceptor switch anticipates the disease Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Disease and space position 2 possible scenarios: immune system fail precedes highly mutated viruses only in the coreceptor switch cases of low CD4+ cell count coreceptor switch anticipates the disease Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Disease and space position 2 possible scenarios: immune system fail precedes highly mutated viruses only in the coreceptor switch cases of low CD4+ cell count coreceptor switch anticipates the disease Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Disease and space position 2 possible scenarios: immune system fail precedes highly mutated viruses only in the coreceptor switch cases of low CD4+ cell count coreceptor switch anticipates the disease mutated viruses within all levels of CD4+ cell count Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Disease and space position Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Disease and space position Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Conclusions conservation of CCR5 V3 loop sequences highly variable CXCR4 viruses association to the immune escape scenario Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008
Conclusion Acknowledgements Alexander Thielen Rolf Kaiser Oliver Sander Saleta Sierra Aragon André Altmann Thomas Lengauer
Recommend
More recommend
