Biology subjects

De Maio, N.

Publications and source records attributed to De Maio, N..

3 recordsLinked to original sources

bioRxiv2017

Bayesian Reconstruction of Transmission within Outbreaks using Genomic Variants

Pathogen genome sequencing can reveal details of transmission histories and is a powerful tool in the fight against infectious disease. In particular, within-host pathogen genomic variants identified through heterozygous nucleotide base calls are a potential source of information to identify linked cases and infer direction and time of transmission. However, using such data effectively to model disease transmission presents a number of challenges, including differentiating genuine variants from those observed due to sequencing error, as well as the specification of a realistic model for within-host pathogen population dynamics.\n\nHere we propose a new Bayesian approach to transmission inference, BadTrIP (BAyesian epiDemiological TRansmission Inference from Polymorphisms), that explicitly models evolution of pathogen populations in an outbreak, transmission (including transmission bottlenecks), and sequencing error. BadTrIP enables the inference of host-to-host transmission from pathogen sequencing data and epidemiological data. By assuming that genomic variants are unlinked, our method does not require the computationally intensive and unreliable reconstruction of individual haplotypes. Using simulations we show that BadTrIP is robust in most scenarios and can accurately infer transmission events by efficiently combining information from genetic and epidemiological sources; thanks to its realistic model of pathogen evolution and the inclusion of epidemiological data, BadTrIP is also more accurate than existing approaches. BadTrIP is distributed as an open source package (https://bitbucket.org/nicofmay/badtrip) for the phylogenetic software BEAST2.\n\nWe apply our method to reconstruct transmission history at the early stages of the 2014 Ebola outbreak, showcasing the power of within-host genomic variants to reconstruct transmission events.\n\nAuthor SummaryWe present a new tool to reconstruct transmission events within outbreaks. Our approach makes use of pathogen genetic information, notably genetic variants at low frequency within host that are usually discarded, and combines it with epidemiological information of host exposure to infection. This leads to accurate reconstruction of transmission even in cases where abundant within-host pathogen genetic variation and weak transmission bottlenecks (multiple pathogen units colonising a new host at transmission) would otherwise make inference difficult due to the transmission history differing from the pathogen evolution history inferred from pathogen isolets. Also, the use of within-host pathogen genomic variants increases the resolution of the reconstruction of the transmission tree even in scenarios with limited within-outbreak pathogen genetic diversity: within-host pathogen populations that appear identical at the level of consensus sequences can be discriminated using within-host variants. Our Bayesian approach provides a measure of the confidence in different possible transmission histories, and is published as open source software. We show with simulations and with an analysis of the beginning of the 2014 Ebola outbreak that our approach is applicable in many scenarios, improves our understanding of transmission dynamics, and will contribute to finding and limiting sources and routes of transmission, and therefore preventing the spread of infectious disease.

genetics↗

bioRxiv2017

Frequent recombination of pneumococcal capsule highlights future risks of emergence of novel serotypes.

Capsular diversity of Streptococcus pneumoniae constitutes a major obstacle in eliminating the pneumococcal disease. Such diversity is genetically encoded by almost 100 variants of the capsule polysaccharide locus (cps). However, the evolutionary dynamics of the capsule - the target of the currently used vaccines - remains not fully understood. Here, using genetic data from 4,469 bacterial isolates, we found cps to be an evolutionary hotspot with elevated substitution and recombination rates. These rates were a consequence of altered selection at this locus, supporting the hypothesis that the capsule has an increased potential to generate novel diversity compared to the rest of the genome. Analysis of twelve serogroups revealed their complex evolutionary history, which was principally driven by recombination with other serogroups and other streptococci. We observed significant variation in recombination rates between different serogroups. This variation could only be partially explained by the lineage-specific recombination rate, the remaining factors being likely driven by serogroup-specific ecology and epidemiology. Finally, we discovered two previously unobserved mosaic serotypes in the densely sampled collection from Mae La, Thailand, here termed 10X and 21X. Our results thus emphasise the strong adaptive potential of the bacterium by its ability to generate novel serotypes by recombination.

evolutionary biology↗

bioRxiv2016

The Bacterial Sequential Markov Coalescent

Bacteria can exchange and acquire new genetic material from other organisms directly and via the environment. This process, known as bacterial recombination, has a strong impact on the evolution of bacteria, for example leading to the spread of antibiotic resistance across clades and species, and to the avoidance of clonal interference. Recombination hinders phylogenetic and transmission inference because it creates patterns of substitutions that are not consistent with the hypothesis of a single evolutionary tree (homoplasies). Bacterial recombination is typically modelled as statistically akin to the gene conversion process of eukaryotes, i.e., using the coalescent with gene conversion (CGC). However, this model can be very computationally demanding as it requires to account for the correlations of evolutionary histories of even distant loci. So, with the increasing popularity of whole genome sequencing, the need has emerged for a new and faster approach to model and simulate bacterial evolution at genomic scales. We present a new model that approximates the coalescent with gene conversion: the bacterial sequential Markov coalescent (BSMC). Our approach is based on a similar idea to the the sequential Markov coalescent (SMC), an approximation of the coalescent with recombination. However, bacterial recombination poses hurdles to a sequential Markov approximation, as it leads to strong correlations and linkage disequilibrium across very distant sites in the genome. Our BSMC overcomes these difficulties and shows both a considerable reduction in computational demand compared the exact CGC, and very similar patterns in the simulated data. We use the BSMC within an Approximate Bayesian Computation (ABC) inference scheme and show that we can correctly recover parameters simulated under the exact CGC, which further showcases the accuracy of our approximation. We also use this ABC approach to infer recombination rate, mutation rate, and recombination tract length from a whole genome alignment of Bacillus cereus. Lastly, we implemented our BSMC model within a new simulation software FastSimBac. In addition to the decreased computational demand compared to previous bacterial genome evolution simulators, FastSimBac also provides a much more general set of options for evolutionary scenarios, allowing population structure with migration, speciations, population size changes, and recombination hotspots. FastSimBac is available from https://bitbucket.org/nicofmay/fastsimbac and is distributed as open source under the terms of the GNU General Public Licence.

evolutionary biology↗