Imperial College London

DrXavierDidelot

Faculty of MedicineSchool of Public Health

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3622x.didelot

 
 
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Location

 

G30Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

150 results found

Hennart M, Panunzi LG, Rodrigues C, Gaday Q, Baines SL, Barros-Pinkelnig M, Carmi-Leroy A, Dazas M, Wehenkel AM, Didelot X, Toubiana J, Badell E, Brisse Set al., 2020, Population genomics and antimicrobial resistance in Corynebacterium diphtheriae, GENOME MEDICINE, Vol: 12, ISSN: 1756-994X

Journal article

Zhao L, Chen H, Didelot X, Li Z, Li Y, Chen M, Du Y, Zhao H, Li J, Hu Q, Kan B, Chen M, Pang Bet al., 2020, Co-existence of multiple distinct lineages in Vibrio parahaemolyticus serotype O4:K12., Microb Genom, Vol: 6

Vibrio parahaemolyticus is an important cause of foodborne gastroenteritis globally. Thermostable direct haemolysin (TDH) and the TDH-related haemolysin are the two key virulence factors in V. parahaemolyticus. Vibrio pathogenicity islands harbour the genes encoding these two haemolysins. The serotyping of V. parahaemolyticus is based on the combination of O and K antigens. Frequent recombination has been observed in V. parahaemolyticus, including in the genomic regions encoding the O and K antigens. V. parahaemolyticus serotype O4:K12 has caused gastroenteritis outbreaks in the USA and Spain. Recently, outbreaks caused by this serotype of V. parahaemolyticus have been reported in China. However, the relationships among this serotype of V. parahaemolyticus strains isolated in different regions have not been addressed. Here, we investigated the genome variation of the V. parahaemolyticus serotype O4:K12 using the whole-genome sequences of 29 isolates. We determined five distinct lineages in this strain collection. We observed frequent recombination among different lineages. In contrast, little recombination was observed within each individual lineage. We showed that the lineage of this serotype of V. parahaemolyticus isolated in America was different from those isolated in Asia and identified genes that exclusively existed in the strains isolated in America. Pan-genome analysis showed that strain-specific and cluster-specific genes were mostly located in the genomic islands. Pan-genome analysis also showed that the vast majority of the accessory genes in the O4:K12 serotype of V. parahaemolyticus were acquired from within the genus Vibrio. Hence, we have shown that multiple distinct lineages exist in V. parahaemolyticus serotype O4:K12 and have provided more evidence about the gene segregation found in V. parahaemolyticus isolated in different continents.

Journal article

Osnes MN, Didelot X, Korne-Elenbaas JD, Alfsnes K, Brynildsrud OB, Syversen G, Nilsen ØJ, De Blasio BF, Caugant DA, Eldholm Vet al., 2020, Sudden emergence of a Neisseria gonorrhoeae clade with reduced susceptibility to extended-spectrum cephalosporins, Norway., Microb Genom, Vol: 6

Neisseria gonorrhoeae multilocus sequence type (ST)-7827 emerged in a dramatic fashion in Norway in the period 2016-2018. Here, we aim to shed light on the provenance and expansion of this ST. ST-7827 was found to be polyphyletic, but the majority of members belonged to a monophyletic clade we termed PopPUNK cluster 7827 (PC-7827). In Norway, both PC-7827 and ST-7827 isolates were almost exclusively isolated from men. Phylogeographical analyses demonstrated an Asian origin of the genogroup, with multiple inferred exports to Europe and the USA. The genogroup was uniformly resistant to fluoroquinolones, and associated with reduced susceptibility to both azithromycin and the extended-spectrum cephalosporins (ESCs) cefixime and ceftriaxone. From a genetic background including the penA allele 13.001, associated with reduced ESC susceptibility, we identified repeated events of acquisition of porB alleles associated with further reduction in ceftriaxone susceptibility. Transmission of the strain was significantly reduced in Norway in 2019, but our results indicate the existence of a recently established global reservoir. The worrisome drug-resistance profile and rapid emergence of PC-7827 calls for close monitoring of the situation.

Journal article

Lassalle F, Dastgheib SMM, Zhao F-J, Zhang J, Verbag S, Fruhling A, Brinkmann H, Osborne T, Sikorski J, Balloux F, Didelot X, Santini J, Petersen Jet al., 2020, Phylogenomics reveals the basis of adaptation of Pseudorhizobium species to extreme environments and supports a taxonomic revision of the genus, Systematic and Applied Microbiology, ISSN: 0172-5564

The family Rhizobiaceae includes many genera of soil bacteria, often isolated for their association with plants. Herein, we investigate the genomic diversity of a group of Rhizobium species and unclassified strains isolated from atypical environments, including seawater, rock matrix or polluted soil. Based on whole-genome similarity and core genome phylogeny, we show that this group corresponds to the genus Pseudorhizobium. We thus reclassify Rhizobium halotolerans, R. marinum, R. flavum and R. endolithicum as P. halotolerans sp. nov., P. marinum comb. nov. , P. flavum comb. nov. and P. endolithicum comb. nov. , respectively, and show that P. pelagicum is a synonym of P. marinum . We also delineate a new chemolithoautotroph species, P. banfieldiae sp. nov. , whose type strain is NT-26 T (= DSM 106348 T = CFBP 8663 T ) . This genome-based classification was supported by a chemotaxonomic comparison, with increasing taxonomic resolution provided by fatty acid, protein and metabolic profiles. In addition, we used a phylogenetic approach to infer scenarios of duplication, horizontal transfer and loss for all genes in the Pseudorhizobium pangenome. We thus identify the key functions associated with the diversification of each species and higher clades, shedding light on the mechanisms of adaptation to their respective ecological niches. Respiratory proteins acquired at the origin of Pseudorhizobium were combined with clade-specific genes to enable different strategies for detoxification and nutrition in harsh, nutrient- poor environments.

Journal article

Whittles LK, White PJ, Didelot X, 2020, Assessment of the potential of vaccination to combat antibiotic resistance in gonorrhea: a modeling analysis to determine preferred product characteristics, Clinical Infectious Diseases, Vol: 71, Pages: 1912-1919, ISSN: 1058-4838

BACKGROUND: Gonorrhea incidence is increasing rapidly in many countries, whilst antibiotic resistance is making treatment more difficult. Combined with evidence that MeNZB and Bexsero meningococcal vaccines are likely partially-protective against gonorrhea, this has renewed interest in a gonococcal vaccine, and several candidates are in development. Key questions are how protective a vaccine needs to be, how long protection needs to last, and how should it be targeted. We assessed vaccination's potential impact, and the feasibility of achieving WHO's target 90% reduction in gonorrhea incidence 2016-2030, by comparing realistic vaccination strategies under a range of scenarios of vaccine efficacy and duration of protection, and emergence of extensively-resistant gonorrhea. METHODS: We developed a stochastic transmission-dynamic model, incorporating asymptomatic and symptomatic infection and heterogeneous sexual behavior in men-who-have-sex-with-men (MSM). We used data from England, which has a comprehensive, consistent nationwide surveillance system. Using particle Markov Chain Monte Carlo methods we fitted the model to gonorrhea incidence in 2008-17, and then used Bayesian forecasting to examine an extensive range of scenarios. RESULTS: Even in the worst-case scenario of untreatable infection emerging, the WHO target is achievable if all MSM attending sexual health clinics receive a vaccine offering ≥52% protection for ≥6 years. A vaccine conferring 31% protection (as estimated for MeNZB) for 2-4 years, could reduce incidence in 2030 by 45% in the worst-case scenario, and by 75% if >70% of resistant gonorrhea remains treatable. CONCLUSIONS: Even a partially-protective vaccine, delivered through a realistic targeting strategy, could substantially reduce gonorrhea incidence, despite antibiotic resistance.

Journal article

Wang L, Didelot X, Yang J, Wong G, Shi Y, Liu W, Gao GF, Bi Yet al., 2020, Inference of person-to-person transmission of COVID-19 reveals hidden super-spreading events during the early outbreak phase, NATURE COMMUNICATIONS, Vol: 11, ISSN: 2041-1723

Journal article

Janezic S, Dingle K, Alvin J, Accetto T, Didelot X, Crook DW, Lacy DB, Rupnik Met al., 2020, Comparative genomics of Clostridioides difficile toxinotypes identifies module-based toxin gene evolution, MICROBIAL GENOMICS, Vol: 6, ISSN: 2057-5858

Journal article

Volz E, Wiuf C, Grad YH, Frost SDW, Dennis AM, Didelot Xet al., 2020, Identification of hidden population structure in time-scaled phylogenies, Systematic Biology, Vol: 69, Pages: 884-896, ISSN: 1063-5157

Abstract Population structure influences genealogical patterns, however data pertaining to how populations are structured are often unavailable or not directly observable. Inference of population structure is highly important in molecular epidemiology where pathogen phylogenetics is increasingly used to infer transmission patterns and detect outbreaks. Discrepancies between observed and idealised genealogies, such as those generated by the coalescent process, can be quantified, and where significant differences occur, may reveal the action of natural selection, host population structure, or other demographic and epidemiological heterogeneities. We have developed a fast non-parametric statistical test for detection of cryptic population structure in time-scaled phylogenetic trees. The test is based on contrasting estimated phylogenies with the theoretically expected phylodynamic ordering of common ancestors in two clades within a coalescent framework. These statistical tests have also motivated the development of algorithms which can be used to quickly screen a phylogenetic tree for clades which are likely to share a distinct demographic or epidemiological history. Epidemiological applications include identification of outbreaks in vulnerable host populations or rapid expansion of genotypes with a fitness advantage. To demonstrate the utility of these methods for outbreak detection, we applied the new methods to large phylogenies reconstructed from thousands of HIV-1 partial pol sequences. This revealed the presence of clades which had grown rapidly in the recent past, and was significantly concentrated in young men, suggesting recent and rapid transmission in that group. Furthermore, to demonstrate the utility of these methods for the study of antimicrobial resistance, we applied the new methods to a large phylogeny reconstructed from whole genome Neisseria gonorrhoeae sequences. We find that population structure detected using these methods closely overlaps with th

Journal article

Didelot X, Siveroni I, Volz EM, 2020, Additive uncorrelated relaxed clock models for the dating of genomic epidemiology phylogenies, Molecular Biology and Evolution, ISSN: 0737-4038

Phylogenetic dating is one of the most powerful and commonly used methods of drawing epidemiological interpretations from pathogen genomic data. Building such trees requires considering a molecular clock model which represents the rate at which substitutions accumulate on genomes. When the molecular clock rate is constant throughout the tree then the clock is said to be strict, but this is often not an acceptable assumption. Alternatively, relaxed clock models consider variations in the clock rate, often based on a distribution of rates for each branch. However, we show here that the distributions of rates across branches in commonly used relaxed clock models are incompatible with the biological expectation that the sum of the numbers of substitutions on two neighbouring branches should be distributed as the substitution number on a single branch of equivalent length. We call this expectation the additivity property. We further show how assumptions of commonly used relaxed clock models can lead to estimates of evolutionary rates and dates with low precision and biased confidence intervals. We therefore propose a new additive relaxed clock model where the additivity property is satisfied. We illustrate the use of our new additive relaxed clock model on a range of simulated and real datasets, and we show that using this new model leads to more accurate estimates of mean evolutionary rates and ancestral dates.

Journal article

Fountain-Jones NM, Appaw RC, Carver S, Didelot X, Volz E, Charleston Met al., 2020, Emerging phylogenetic structure of the SARS-CoV-2 pandemic., Virus Evol, Vol: 6, ISSN: 2057-1577

Since spilling over into humans, SARS-CoV-2 has rapidly spread across the globe, accumulating significant genetic diversity. The structure of this genetic diversity and whether it reveals epidemiological insights are fundamental questions for understanding the evolutionary trajectory of this virus. Here, we use a recently developed phylodynamic approach to uncover phylogenetic structures underlying the SARS-CoV-2 pandemic. We find support for three SARS-CoV-2 lineages co-circulating, each with significantly different demographic dynamics concordant with known epidemiological factors. For example, Lineage C emerged in Europe with a high growth rate in late February, just prior to the exponential increase in cases in several European countries. Non-synonymous mutations that characterize Lineage C occur in functionally important gene regions responsible for viral replication and cell entry. Even though Lineages A and B had distinct demographic patterns, they were much more difficult to distinguish. Continuous application of phylogenetic approaches to track the evolutionary epidemiology of SARS-CoV-2 lineages will be increasingly important to validate the efficacy of control efforts and monitor significant evolutionary events in the future.

Journal article

Lassalle F, Didelot X, 2020, Bacterial microevolution and the pangenome, The Pangenome: Diversity, Dynamics and Evolution of Genomes, Pages: 129-149, ISBN: 9783030382803

© The Author(s) 2020. The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history.

Book chapter

Ledda A, Cummins M, Shaw LP, Jauneikaite E, Cole K, Lasalle F, Barry D, Rosmarin C, Anaraki S, Wareham D, Stoesser N, Paul J, Manuel R, Cherian BP, Didelot Xet al., 2020, Hospital outbreak of carbapenem-resistant Enterobacteriales associated with an OXA-48 plasmid carried mostly by Escherichia coli ST399

<jats:title>Abstract</jats:title><jats:p>A hospital outbreak of carbapenem-resistant Enterobacteriales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous OXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacteriales were involved in the outbreak. <jats:italic>Escherichia coli</jats:italic> ST399 accounted for 20/55 of all the isolates. Comparative genomics with publicly available <jats:italic>E. coli</jats:italic> ST399 sequence data showed that the outbreak isolates formed a unique clade. The OXA-48 plasmid identified in the outbreak differed from other known plasmids by an estimated five homologous recombination events. We estimated a lower bound to the plasmid conjugation rate to be 0.23 conjugation events per lineage per year. Our analysis suggests co-evolution between the plasmid and its main bacterial host to be a key driver of the outbreak. This is the first study to report carbapenem-resistant <jats:italic>E. coli</jats:italic> ST399 carrying OXA48 as the main cause of a plasmid-borne outbreak within a hospital setting. This study supports complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.</jats:p>

Journal article

Rodriguez Manzano J, Moser N, Malpartida Cardenas K, Moniri A, Fisarova L, Pennisi I, Boonyasiri A, Jauneikaite E, Abdolrasouli A, Otter J, Bolt F, Davies F, Didelot X, Holmes A, Georgiou Pet al., 2020, Rapid detection of mobilized colistin resistance using a nucleic acid based lab-on-a-chip diagnostic system, Scientific Reports, Vol: 10, ISSN: 2045-2322

The increasing prevalence of antimicrobial resistance is a serious threat to global public health. One of the most concerning trends is the rapid spread of Carbapenemase-Producing Organisms (CPO), where colistin has become the last-resort antibiotic treatment. The emergence of colistin resistance, including the spread of mobilized colistin resistance (mcr) genes, raises the possibility of untreatable bacterial infections and motivates the development of improved diagnostics for the detection of colistin-resistant organisms. This work demonstrates a rapid response for detecting the most recently reported mcr gene, mcr−9, using a portable and affordable lab-on-a-chip (LoC) platform, offering a promising alternative to conventional laboratory-based instruments such as real-time PCR (qPCR). The platform combines semiconductor technology, for non-optical real-time DNA sensing, with a smartphone application for data acquisition, visualization and cloud connectivity. This technology is enabled by using loop-mediated isothermal amplification (LAMP) as the chemistry for targeted DNA detection, by virtue of its high sensitivity, specificity, yield, and manageable temperature requirements. Here, we have developed the first LAMP assay for mcr−9 - showing high sensitivity (down to 100 genomic copies/reaction) and high specificity (no cross-reactivity with other mcr variants). This assay is demonstrated through supporting a hospital investigation where we analyzed nucleic acids extracted from 128 carbapenemase-producing bacteria isolated from clinical and screening samples and found that 41 carried mcr−9 (validated using whole genome sequencing). Average positive detection times were 6.58 ± 0.42 min when performing the experiments on a conventional qPCR instrument (n = 41). For validating the translation of the LAMP assay onto a LoC platform, a subset of the samples were tested (n = 20), showing average detection times o

Journal article

Vegvari C, Grad Y, White P, Didelot X, Whittles L, Scangarella-Oman N, Mitrani-Gold F, Dumont E, Perry C, Gilchrist K, Hossain M, Mortimer T, Anderson R, Gardiner Det al., 2020, Using rapid point-of-care tests to inform antibiotic choice to mitigate drug resistance in gonorrhoea, Eurosurveillance, ISSN: 1025-496X

Journal article

Wang H, Yang C, Sun Z, Zheng W, Zhang W, Yu H, Wu Y, Didelot X, Yang R, Pan J, Cui Yet al., 2020, Genomic epidemiology of Vibrio cholerae reveals the regional and global spread of two epidemic non-toxigenic lineages, PLOS NEGLECTED TROPICAL DISEASES, Vol: 14, ISSN: 1935-2735

Journal article

Wang H, Yang C, Sun Z, Zheng W, Zhang W, Yu H, Wu Y, Didelot X, Yang R, Pan J, Cui Yet al., 2020, Genomic epidemiology of Vibrio cholerae reveals the regional and global spread of two epidemic non-toxigenic lineages., PLoS Negl Trop Dis, Vol: 14

Non-toxigenic Vibrio cholerae isolates have been found associated with diarrheal disease globally, however, the global picture of non-toxigenic infections is largely unknown. Among non-toxigenic V. cholerae, ctxAB negative, tcpA positive (CNTP) isolates have the highest risk of disease. From 2001 to 2012, 71 infectious diarrhea cases were reported in Hangzhou, China, caused by CNTP serogroup O1 isolates. We sequenced 119 V. cholerae genomes isolated from patients, carriers and the environment in Hangzhou between 2001 and 2012, and compared them with 850 publicly available global isolates. We found that CNTP isolates from Hangzhou belonged to two distinctive lineages, named L3b and L9. Both lineages caused disease over a long time period with usually mild or moderate clinical symptoms. Within Hangzhou, the spread route of the L3b lineage was apparently from rural to urban areas, with aquatic food products being the most likely medium. Both lineages had been previously reported as causing local endemic disease in Latin America, but here we show that global spread of them has occurred, with the most likely origin of L3b lineage being in Central Asia. The L3b lineage has spread to China on at least three occasions. Other spread events, including from China to Thailand and to Latin America were also observed. We fill the missing links in the global spread of the two non-toxigenic serogroup O1 V. cholerae lineages that can cause human infection. The results are important for the design of future disease control strategies: surveillance of V. cholerae should not be limited to ctxAB positive strains.

Journal article

Lassalle F, Veber P, Jauneikaite E, Didelot Xet al., 2019, Automated reconstruction of all gene histories in large bacterial pangenome datasets and search for co-evolved gene modules with Pantagruel

<jats:title>Abstract</jats:title><jats:p>The availability of bacterial pangenome data grows exponentially, requiring efficient new methods of analysis. Currently popular approaches for the fast comparison of genomes have the drawback of not being based on explicit evolutionary models of diversification. Making sense of bacterial genome evolution, and notably in the accessory genome, requires however to take into account the complex processes by which the genomes evolve. Here we present the <jats:italic>Pantagruel</jats:italic> bioinformatic software pipeline, which enables the construction of a complete bacterial pangenome database geared towards the inference of gene evolution scenarios using gene tree/species tree reconciliation. <jats:italic>Pantagruel</jats:italic> is a modular pipeline that combines state-of-the-art external software with unique new methods. It can be executed with no supervision to perform a standard pangenome analysis, or be configured by advanced users to integrate methods of choice. A relational database underlies its data structure, allowing efficient retrieval of the large-scale data generated by integrative analyses of pangenome evolutionary history. From the reconstructed gene evolution scenarios, two main outputs are derived: firstly the gene tree-aware assignation of orthology, allowing the fine analysis of gene gain and loss history over the species phylogeny, and secondly a network of gene-to-gene association based on correlated events in scenarios of gene evolution, leading to the definition of co-evolved gene modules. <jats:italic>Pantagruel</jats:italic> is available as an open source software package at <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://github.com/flass/pantagruel">https://github.com/flass/pantagruel</jats:ext-link>.</jats:p>

Journal article

Lassalle F, Dastgheib SMM, Zhao F-J, Zhang J, Verbarg S, Frühling A, Brinkmann H, Osborne TH, Sikorski J, Balloux F, Didelot X, Santini JM, Petersen Jet al., 2019, Phylogenomic analysis reveals the basis of adaptation of Pseudorhizobium species to extreme environments

<jats:title>Abstract</jats:title><jats:p>The family <jats:italic>Rhizobiaceae</jats:italic> includes many genera of soil bacteria, often isolated for their association with plants. Herein, we investigate the genomic diversity of a group of <jats:italic>Rhizobium</jats:italic> species and unclassified strains isolated from atypical environments, including seawater, rock matrix or polluted soil. Based on whole-genome similarity and core genome phylogeny, we show that this group corresponds to the genus <jats:italic>Pseudorhizobium.</jats:italic> We thus reclassify <jats:italic>Rhizobium halotolerans, R. marinum, R. flavum</jats:italic> and <jats:italic>R. endolithicum</jats:italic> as <jats:italic>P. halotolerans</jats:italic> comb. nov., <jats:italic>P. marinum</jats:italic> comb. nov.<jats:italic>, P. flavum</jats:italic> comb. nov. and <jats:italic>R. endolithicum</jats:italic> comb. nov., respectively, and show that <jats:italic>P. pelagicum</jats:italic> is a synonym of <jats:italic>P. marinum</jats:italic>. We also delineate a new chemolithoautotroph species, <jats:italic>P. banfieldiae</jats:italic> sp. nov., whose type strain is NT-26<jats:sup>T</jats:sup> (= DSM 106348<jats:sup>T</jats:sup> = CFBP 8663<jats:sup>T</jats:sup>). This genome-based classification was supported by a chemotaxonomic comparison, with gradual taxonomic resolution provided by fatty acid, protein and metabolic profiles. In addition, we used a phylogenetic approach to infer scenarios of duplication, horizontal transfer and loss for all genes in the <jats:italic>Pseudorhizobium</jats:italic> pangenome. We thus identify the key functions associated with the diversification of each species and higher clades, shedding light on the mechanisms of adaptation to their respective ecological

Journal article

Criscuolo A, Issenhuth-Jeanjean S, Didelot X, Thorell K, Hale J, Parkhill J, Thomson NR, Weill F-X, Falush D, Brisse Set al., 2019, The speciation and hybridization history of the genus Salmonella, MICROBIAL GENOMICS, Vol: 5, ISSN: 2057-5858

Journal article

Volz EM, Wiuf C, Grad YH, Frost SDW, Dennis AM, Didelot Xet al., 2019, Identification of hidden population structure in time-scaled phylogenies, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>Population structure influences genealogical patterns, however data pertaining to how populations are structured are often unavailable or not directly observable. Inference of population structure is highly important in molecular epidemiology where pathogen phylogenetics is increasingly used to infer transmission patterns and detect outbreaks. Discrepancies between observed and idealised genealogies, such as those generated by the coalescent process, can be quantified, and where significant differences occur, may reveal the action of natural selection, host population structure, or other demographic and epidemiological heterogeneities. We have developed a fast non-parametric statistical test for detection of cryptic population structure in time-scaled phylogenetic trees. The test is based on contrasting estimated phylogenies with the theoretically expected phylodynamic ordering of common ancestors in two clades within a coalescent framework. These statistical tests have also motivated the development of algorithms which can be used to quickly screen a phylogenetic tree for clades which are likely to share a distinct demographic or epidemiological history. Epidemiological applications include identification of outbreaks in vulnerable host populations or rapid expansion of genotypes with a fitness advantage. To demonstrate the utility of these methods for outbreak detection, we applied the new methods to large phylogenies reconstructed from thousands of HIV-1 partial <jats:italic>pol</jats:italic> sequences. This revealed the presence of clades which had grown rapidly in the recent past, and was significantly concentrated in young men, suggesting recent and rapid transmission in that group. Furthermore, to demonstrate the utility of these methods for the study of antimicrobial resistance, we applied the new methods to a large phylogeny reconstructed from whole genome <jats:italic>Neisseria go

Working paper

Didelot X, Pouwels KB, 2019, Machine-learning-assisted selection of antibiotic prescription, NATURE MEDICINE, Vol: 25, Pages: 1033-1034, ISSN: 1078-8956

Journal article

Ozer EA, Nnah E, Didelot X, Whitaker RJ, Hauser ARet al., 2019, The Population Structure of Pseudomonas aeruginosa Is Characterized by Genetic Isolation of exoU plus and exoS plus Lineages, GENOME BIOLOGY AND EVOLUTION, Vol: 11, Pages: 1780-1796, ISSN: 1759-6653

Journal article

Ailloud F, Didelot X, Woltemate S, Pfaffinger G, Overmann J, Bader RC, Schulz C, Malfertheiner P, Suerbaum Set al., 2019, Within-host evolution of Helicobacter pylori shaped by niche-specific adaptation, intragastric migrations and selective sweeps, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723

Journal article

Moniri A, Rodriguez-Manzano J, Malpartida-Cardenas K, Yu L-S, Didelot X, Holmes A, Georgiou Pet al., 2019, Framework for DNA quantification and outlier detection using multidimensional standard curves, Analytical Chemistry, Vol: 91, Pages: 7426-7434, ISSN: 0003-2700

Real-time PCR is a highly sensitive and powerful technology for the quantification of DNA and has become the method of choice in microbiology, bioengineering, and molecular biology. Currently, the analysis of real-time PCR data is hampered by only considering a single feature of the amplification profile to generate a standard curve. The current “gold standard” is the cycle-threshold (Ct) method which is known to provide poor quantification under inconsistent reaction efficiencies. Multiple single-feature methods have been developed to overcome the limitations of the Ct method; however, there is an unexplored area of combining multiple features in order to benefit from their joint information. Here, we propose a novel framework that combines existing standard curve methods into a multidimensional standard curve. This is achieved by considering multiple features together such that each amplification curve is viewed as a point in a multidimensional space. Contrary to only considering a single-feature, in the multidimensional space, data points do not fall exactly on the standard curve, which enables a similarity measure between amplification curves based on distances between data points. We show that this framework expands the capabilities of standard curves in order to optimize quantification performance, provide a measure of how suitable an amplification curve is for a standard, and thus automatically detect outliers and increase the reliability of quantification. Our aim is to provide an affordable solution to enhance existing diagnostic settings through maximizing the amount of information extracted from conventional instruments.

Journal article

Eyre DW, Didelot X, Buckley AM, Freeman J, Moura IB, Crook DW, Peto TEA, SarahWalker A, Wilcox MH, Dingle KEet al., 2019, Clostridium difficile trehalose metabolism variants are common and not associated with adverse patient outcomes when variably present in the same lineage, EBIOMEDICINE, Vol: 43, Pages: 347-355, ISSN: 2352-3964

Journal article

van Dorp L, Wang Q, Shaw LP, Acman M, Brynildsrud OB, Eldholm V, Wang R, Gao H, Yin Y, Chen H, Ding C, Farrer RA, Didelot X, Balloux F, Wang Het al., 2019, Rapid phenotypic evolution in multidrug-resistant Klebsiella pneumoniae hospital outbreak strains, MICROBIAL GENOMICS, Vol: 5, ISSN: 2057-5858

Journal article

Whittles L, White P, Didelot X, 2019, A dynamic power-law sexual network model of gonorrhoea outbreaks, PLoS Computational Biology, Vol: 15, ISSN: 1553-734X

Human networks of sexual contacts are dynamic by nature, with partnerships forming and breaking continuously over time. Sexual behaviours are also highly heterogeneous, so that the number of partners reported by individuals over a given period of time is typically distributed as a power-law. Both the dynamism and heterogeneity of sexual partnerships are likely to have an effect in the patterns of spread of sexually transmitted diseases. To represent these two fundamental properties of sexual networks, we developed a stochastic process of dynamic partnership formation and dissolution, which results in power-law numbers of partners over time. Model parameters can be set to produce realistic conditions in terms of the exponent of the power-law distribution, of the number of individuals without relationships and of the average duration of relationships. Using an outbreak of antibiotic resistant gonorrhoea amongst men have sex with men as a case study, we show that our realistic dynamic network exhibits different properties compared to the frequently used static networks or homogeneous mixing models. We also consider an approximation to our dynamic network model in terms of a much simpler branching process. We estimate the parameters of the generation time distribution and offspring distribution which can be used for example in the context of outbreak reconstruction based on genomic data. Finally, weinvestigate the impact of a range of interventions against gonorrhoea, including increased condom use, more frequent screening and immunisation, concluding that the latter shows great promise to reduce the burden of gonorrhoea, even if the vaccine was only partially effective or applied to only a random subset of the population.

Journal article

Dingle KE, Didelot X, Quan TP, Eyre DW, Stoesser N, Marwick CA, Coia J, Brown D, Buchanan S, Ijaz UZ, Goswami C, Douce G, Fawley WN, Wilcox MH, Peto TEA, Walker AS, Crook DWet al., 2019, A Role for Tetracycline Selection in Recent Evolution of Agriculture-Associated Clostridium difficile PCR Ribotype 078, MBIO, Vol: 10, ISSN: 2150-7511

Journal article

Didelot X, Croucher NJ, Bentley SD, Harris SR, Wilson DJet al., 2018, Bayesian inference of ancestral dates on bacterial phylogenetic trees, Nucleic Acids Research, Vol: 46, Pages: 1-11, ISSN: 0305-1048

The sequencing and comparative analysis of a collection of bacterial genomes from a single species or lineage of interest can lead to key insights into its evolution, ecology or epidemiology. The tool of choice for such a study is often to build a phylogenetic tree, and more specifically when possible a dated phylogeny, in which the dates of all common ancestors are estimated. Here, we propose a new Bayesian methodology to construct dated phylogenies which is specifically designed for bacterial genomics. Unlike previous Bayesian methods aimed at building dated phylogenies, we consider that the phylogenetic relationships between the genomes have been previously evaluated using a standard phylogenetic method, which makes our methodology much faster and scalable. This two-step approach also allows us to directly exploit existing phylogenetic methods that detect bacterial recombination, and therefore to account for the effect of recombination in the construction of a dated phylogeny. We analysed many simulated datasets in order to benchmark the performance of our approach in a wide range of situations. Furthermore, we present applications to three different real datasets from recent bacterial genomic studies. Our methodology is implemented in a R package called BactDating which is freely available for download at https://github.com/xavierdidelot/BactDating.

Journal article

Meric G, Mageiros L, Pensar J, Laabei M, Yahara K, Pascoe B, Kittiwan N, Tadee P, Post V, Lamble S, Bowden R, Bray JE, Morgenstern M, Jolley KA, Maiden MCJ, Feil EJ, Didelot X, Miragaia M, de Lencastre H, Moriarty TF, Rohde H, Massey R, Mack D, Corander J, Sheppard SKet al., 2018, Disease-associated genotypes of the commensal skin bacterium Staphylococcus epidermidis, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723

Journal article

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