V3 Loop Sequence Space Analysis Kasia Bo ek bozek@mpi-inf.mpg.de - - PowerPoint PPT Presentation

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V3 Loop Sequence Space Analysis Kasia Bo ek bozek@mpi-inf.mpg.de Max-Planck Institute fr Informatik, Saarbrcken AREVIR Bonn 24.04.2009 V3 loop sequence space analysis selection of V3 loop sequence variants for experimental imaging of

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V3 Loop Sequence Space Analysis

Kasia Bożek bozek@mpi-inf.mpg.de Max-Planck Institute für Informatik, Saarbrücken

AREVIR Bonn 24.04.2009

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Kasia Bożek AREVIR Bonn 24.04.2008

V3 loop sequence space analysis

selection of V3 loop sequence variants for experimental imaging of the HIV cell entry understanding of the distribution of V3 loop sequences in their sequence space

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Approach

2 sets of sequences from Los Alamos NSI/ SI CCR5/ CXCR4/ R5X4 distance distribution phylogenetical analysis using Splitstree hierarchical clustering

Data analysis

Kasia Bożek AREVIR Bonn 24.04.2008

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NSI-NSI

Distance distribution – NSI/ SI

Kasia Bożek AREVIR Bonn 24.04.2008

NSI-SI SI-SI

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Distance distribution – R5/ X4

Kasia Bożek AREVIR Bonn 24.04.2008

R5-R5 R5X4-R5X4 X4-X4

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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

Phylogenetical analysis - Splitstree

Kasia Bożek AREVIR Bonn 24.04.2008

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Phylogenetical analysis

Kasia Bożek AREVIR meeting Bonn 24.04.2008

Phylogenetical analysis - Splitstree

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Hierarchical clustering

Kasia Bożek AREVIR Bonn 24.04.2008

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NSI R5 SI X4 R5X4

Kasia Bożek AREVIR Bonn 24.04.2008

Hierarchical clustering

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R5/ NSI: conserved forming clusters slow disease progression

V3 loop sequence space analysis

immune component of the V3 loop evolutionary pattern? R5/ NSI sequences under purifying selection of the immune system?

Kasia Bożek AREVIR Bonn 24.04.2008

X4/ SI: diverse placed in distant parts of sequence space disease

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Sequence space location vs. CD4+ T-cells

Kasia Bożek AREVIR Bonn 24.04.2008

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Kasia Bożek AREVIR Bonn 24.04.2008

Sequence space location vs. CD4+ T-cells

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conservation of CCR5/ NSI V3 loop sequences high variability of CXCR4/ SI viruses possible immune system selection pressure

Kasia Bożek AREVIR Bonn 24.04.2008

Conclusions

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Conclusion

Alexander Thielen Oliver Sander André Altmann Thomas Lengauer

Acknowledgements

Rolf Kaiser Saleta Sierra Aragon

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