arXiv subjects

Daniel J Wilson

Publications and source records attributed to Daniel J Wilson.

3 recordsLinked to original sources

arXiv2019

Sequential Monte Carlo with transformations

This paper introduces methodology for performing Bayesian inference sequentially on a sequence of posteriors on spaces of different dimensions. We show how this may be achieved through the use of sequential Monte Carlo (SMC) samplers (Del Moral et al., 2006, 2007), making use of the full flexibility of this framework in order that the method is computationally efficient. In particular, we introduce the innovation of using deterministic transformations to move particles effectively between target distributions with different dimensions. This approach, combined with adaptive methods, yields an extremely flexible and general algorithm for Bayesian model comparison that is suitable for use in applications where the acceptance rate in reversible jump Markov chain Monte Carlo (RJMCMC) is low. We demonstrate this approach on the well-studied problem of model comparison for mixture models, and for the novel application of inferring coalescent trees sequentially, as data arrives.

stat.CO↗

arXiv2016

SCOTTI: Efficient Reconstruction of Transmission within Outbreaks with the Structured Coalescent

Exploiting pathogen genomes to reconstruct transmission represents a powerful tool in the fight against infectious disease. However, their interpretation rests on a number of simplifying assumptions that regularly ignore important complexities of real data, in particular within-host evolution and non-sampled patients. Here we propose a new approach to transmission inference called SCOTTI (Structured COalescent Transmission Tree Inference). This method is based on a statistical framework that models each host as a distinct population, and transmissions between hosts as migration events. Our computationally efficient implementation of this model enables the inference of host-to-host transmission while accommodating within-host evolution and non-sampled hosts. SCOTTI is distributed as an open source package for the phylogenetic software BEAST2. We show that SCOTTI can generally infer transmission events even in the presence of considerable within-host variation, can account for the uncertainty associated with the possible presence of non-sampled hosts, and can efficiently use data from multiple samples of the same host, although there is some reduction in accuracy when samples are collected very close to the infection time. We illustrate the features of our approach by investigating transmission from genetic and epidemiological data in a Foot and Mouth Disease Virus (FMDV) veterinary outbreak in England and a Klebsiella pneumoniae outbreak in a Nepali neonatal unit. Transmission histories inferred with SCOTTI will be important in devising effective measures to prevent and halt transmission.

q-bio.PE↗

arXiv2016

Identifying lineage effects when controlling for population structure improves power in bacterial association studies

Bacteria pose unique challenges for genome-wide association studies (GWAS) because of strong structuring into distinct strains and substantial linkage disequilibrium across the genome. While methods developed for human studies can correct for strain structure, this risks considerable loss- of-power because genetic differences between strains often contribute substantial phenotypic variability. Here we propose a new method that captures lineage-level associations even when locus-specific associations cannot be fine-mapped. We demonstrate its ability to detect genes and genetic variants underlying resistance to 17 antimicrobials in 3144 isolates from four taxonomically diverse clonal and recombining bacteria: Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. Strong selection, recombination and penetrance confer high power to recover known antimicrobial resistance mechanisms, and reveal a candidate association between the outer membrane porin nmpC and cefazolin resistance in E. coli. Hence our method pinpoints locus-specific effects where possible, and boosts power by detecting lineage-level differences when fine-mapping is intractable.

q-bio.GN↗