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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

  1. V3 Loop Sequence Space Analysis Kasia Bo ż ek bozek@mpi-inf.mpg.de MPI Saarbrücken AREVIR meeting, Bonn 11.04.2008

  2. 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

  3. Coreceptor prediction in-silico phenotypic assays Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  4. 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

  5. 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

  6. NSI vs. NSI Distance distribution SI vs. SI NSI vs. SI Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  7. R5 vs. R5 Distance distribution X4 vs. X4 R5X4 vs. R5X4 Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  8. Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  9. Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  10. Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  11. Sequence clustering Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  12. Sequence clustering NSI R5 R5X4 SI X4 Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  13. 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

  14. Phylogenetical analysis Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  15. Phylogenetical analysis split Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  16. Phylogenetical analysis SI NSI Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  17. Phylogenetical analysis Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  18. Phylogenetical analysis Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  19. Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  20. Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  21. Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  22. Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  23. Difficult sequences unexpected placement of some sequences on the tree bad annotation? difficult cases? Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  24. Difficult sequences Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. Disease and space position Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  32. Disease and space position Kasia Bo ż ek AREVIR meeting Bonn 11.04.2008

  33. 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

  34. Conclusion Acknowledgements Alexander Thielen Rolf Kaiser Oliver Sander Saleta Sierra Aragon André Altmann Thomas Lengauer

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