title: Two-phase importance sampling for inference about transmission trees.
abstract: There has been growing interest in the statistics community to develop methods for inferring transmission pathways of infectious pathogens from molecular sequence data. For many datasets, the computational challenge lies in the huge dimension of the missing data. Here, we introduce an importance sampling scheme in which the transmission trees and phylogenies of pathogens are both sampled from reasonable importance distributions, alleviating the inference. Using this approach, arbitrary models of transmission could be considered, contrary to many earlier proposed methods. We illustrate the scheme by analysing transmissions of Streptococcus pneumoniae from household to household within a refugee camp, using data in which only a fraction of hosts is observed, but which is still rich enough to unravel the within-household transmission dynamics and pairs of households between whom transmission is plausible. We observe that while probability of direct transmission is low even for the most prominent cases of transmission, still those pairs of households are geographically much closer to each other than expected under random proximity.
authors.affiliation: Department of Mathematics and Statistics, University of Helsinki, PO Box 68, 00014 Helsinki, Finland elina.numminen@helsinki.fi.
authors.forename: Elina
authors.initials: E
authors.lastname: Numminen
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Chewapreecha
authors.affiliation: Department of Biosciences, University of Helsinki, PO Box 56, 00014 Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Sirén
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sod, Thailand Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Turner
authors.affiliation: Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sod, Thailand Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Turner
authors.affiliation: Department of Biosciences, University of Helsinki, PO Box 56, 00014 Helsinki, Finland Department of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: Department of Mathematics and Statistics, University of Helsinki, PO Box 68, 00014 Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
mesh_terms: D000328:Adult; D001699:Biometry; D004269:DNA, Bacterial; D018562:Disease Transmission, Infectious; D005191:Family Characteristics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D010802:Phylogeny; D011008:Pneumococcal Infections / Q000453:epidemiology*; D012036:Refugees; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000302:isolation & purification; D013785:Thailand
chemical_list: D004269:DNA, Bacterial
keywords: Streptococcus pneumonia; molecular epidemiology; transmission tree