HIV epidemiology Routes of infection MSM: Men who have sex with men - PowerPoint PPT Presentation

Phylogeny-based HIV transmission networks Prabhav Kalaghatgi Max Planck Institute for Informatics AREVIR, May 8 2015 eu resist

HIV epidemiology Routes of infection MSM: Men who have sex with men Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 2/18

HIV epidemiology Routes of infection MSM: Men who have sex with men HET: Heterosexual partners Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 2/18

HIV epidemiology Routes of infection MSM: Men who have sex with men HET: Heterosexual partners IDU: Injection drug users Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 2/18

HIV epidemiology Routes of infection MSM: Men who have sex with men HET: Heterosexual partners IDU: Injection drug users Motivation A better understanding of the HIV epidemic through the analysis of person-to-person transmission network. Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 2/18

Rapidly evolving pathogens Accumulation of genomic mutations via a series of transmissions 6 4 1 2 3 5 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 3/18

Rapidly evolving pathogens Accumulation of genomic mutations via a series of transmissions 6 4 1 2 3 5 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 3/18

Rapidly evolving pathogens Accumulation of genomic mutations via a series of transmissions 6 4 1 2 3 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 3/18

Rapidly evolving pathogens Accumulation of genomic mutations via a series of transmissions 4 1 2 3 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC 4 ATAGGTCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGGCCACCATAC Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 3/18

Rapidly evolving pathogens Accumulation of genomic mutations via a series of transmissions 4 1 2 3 5 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC 4 ATAGGTCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGGCCACCATAC 5 ATAGGTCCATAGCCAGATTGCCCAAATGGATCCACCAGACTGGCCACCATAC Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 3/18

Rapidly evolving pathogens Accumulation of genomic mutations via a series of transmissions 4 6 1 2 3 5 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC 4 ATAGGTCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGGCCACCATAC 5 ATAGGTCCATAGCCAGATTGCCCAAATGGATCCACCAGACTGGCCACCATAC 6 ATAGATCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGCCCACCATAC Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 3/18

Objective Recover transmission network from sequences sampled from infected individuals 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC 4 ATAGGTCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGGCCACCATAC 5 ATAGGTCCATAGCCAGATTGCCCAAATGGATCCACCAGACTGGCCACCATAC 6 ATAGATCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGCCCACCATAC Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 4/18

Objective Recover transmission network from sequences sampled from infected individuals 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC 4 ATAGGTCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGGCCACCATAC 5 ATAGGTCCATAGCCAGATTGCCCAAATGGATCCACCAGACTGGCCACCATAC 6 ATAGATCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGCCCACCATAC 4 6 1 2 5 3 Fully resolved network Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 4/18

Objective Recover transmission network from sequences sampled from infected individuals 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC 4 ATAGGTCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGGCCACCATAC 5 ATAGGTCCATAGCCAGATTGCCCAAATGGATCCACCAGACTGGCCACCATAC 6 ATAGATCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGCCCACCATAC infeasible 4 6 1 2 5 3 Fully resolved network Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 4/18

Objective Recover transmission network from sequences sampled from infected individuals 1 ATAGGTCCATAGCCAGATTGGCCAAATAGATCCACCAGATTGGCCACCATAC 2 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGATTGGCCACCATAC 3 ATAGGTCCATAGCCAGATTGCCCAAATAGATCCACCAGACTGGCCACCATAC 4 ATAGGTCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGGCCACCATAC 5 ATAGGTCCATAGCCAGATTGCCCAAATGGATCCACCAGACTGGCCACCATAC 6 ATAGATCCATAGCCAGATTGCCCAAATAGAACCGCCAGATTGCCCACCATAC infeasible 4 6 4 6 1 2 1 2 3 5 5 3 Partially resolved network Fully resolved network Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 4/18

HIV sequence data: EuResist Selection criteria Subtype B Country of origin in Europe Oldest sequence per individual Sampling times from 1999 to 2012 Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 5/18

HIV sequence data: EuResist Selection criteria Subtype B Country of origin in Europe Oldest sequence per individual Sampling times from 1999 to 2012 Data used 15,000 sequences Transmission mode: MSM (25 % ), HET (22 % ), IDU (19 % ), Unknown (34 % ) Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 5/18

Outline Threshold-based networks Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 6/18

Outline Threshold-based networks Threshold-free networks using phylogenetic distances Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 6/18

Outline Threshold-based networks Threshold-free networks using phylogenetic distances Timed networks using molecular clock Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 6/18

Europe-wide transmission networks Network constructed by thresholding distance between sequences (LogDet) Kalaghatgi et al. European Workshop on HIV & HCV 2013 Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 7/18

Europe-wide transmission networks Network constructed by thresholding distance between sequences (LogDet) Low cross-country transmission Kalaghatgi et al. European Workshop on HIV & HCV 2013 Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 7/18

Europe-wide transmission networks Network constructed by thresholding distance between sequences (LogDet) Low cross-country transmission Small cluster sizes Kalaghatgi et al. European Workshop on HIV & HCV 2013 Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 7/18

Europe-wide transmission networks Network constructed by thresholding distance between sequences (LogDet) Low cross-country transmission Small cluster sizes 25 % of sequences are linked Kalaghatgi et al. European Workshop on HIV & HCV 2013 Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 7/18

Accurate (tree-based) distances LogDet, TN93, Hamming distance yield inaccurate estimates Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 8/18

Accurate (tree-based) distances LogDet, TN93, Hamming distance yield inaccurate estimates Model-based estimates are more accurate Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 8/18

Accurate (tree-based) distances LogDet, TN93, Hamming distance yield inaccurate estimates Model-based estimates are more accurate c – Phylogenetic tree d e a b f Phylogenetic tree Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 8/18

Accurate (tree-based) distances LogDet, TN93, Hamming distance yield inaccurate estimates Model-based estimates are more accurate c – Phylogenetic tree d e – Substitution models: a b GTR, HKY f Phylogenetic tree Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 8/18

Accurate (tree-based) distances LogDet, TN93, Hamming distance yield inaccurate estimates Model-based estimates are more accurate c – Phylogenetic tree d e – Substitution models: a b GTR, HKY f – Among-site rate variation model Phylogenetic tree Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 8/18

Accurate (tree-based) distances LogDet, TN93, Hamming distance yield inaccurate estimates Model-based estimates are more accurate c – Phylogenetic tree d e – Substitution models: a b GTR, HKY f – Among-site rate variation model Phylogenetic tree Optimize models and phylogenetic tree Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 8/18

Threshold-free networks c d e b f a Phylogenetic tree Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 9/18

Threshold-free networks a _ b _ 3.1 c _ 3.4 4.1 c d _ 9.8 8.5 5.9 e d e _ 6.4 4.2 2.6 6.1 b f _ f 5.3 7.5 5.8 8.6 6.5 a a b c d e f Phylogenetic tree Tree-based distances Phylogeny-based HIV transmission networks Prabhav Kalaghatgi 9/18