Accurate and fast graph-based pangenome annotation and clustering with ggCaller DOI Creative Commons
Samuel Horsfield, Gerry Tonkin‐Hill, Nicholas J. Croucher

и другие.

Genome Research, Год журнала: 2023, Номер 33(9), С. 1622 - 1637

Опубликована: Авг. 24, 2023

Bacterial genomes differ in both gene content and sequence mutations, which underlie extensive phenotypic diversity, including variation susceptibility to antimicrobials or vaccine-induced immunity. To identify quantify important variants, all genes within a population must be predicted, functionally annotated, clustered, representing the “pangenome.” Despite volume of genome data available, prediction annotation are currently conducted isolation on individual genomes, is computationally inefficient frequently inconsistent across genomes. Here, we introduce open-source software graph-gene-caller (ggCaller). ggCaller combines prediction, functional annotation, clustering into single workflow using population-wide de Bruijn graphs, removing redundancy resulting more accurate predictions orthologue clustering. We applied simulated real-world bacterial sets containing hundreds thousands comparing it current state-of-the-art tools. has considerable speed-ups with equivalent greater accuracy, particularly complex sources error, such as assembly contamination fragmentation. also an extension genome-wide association studies, enabling querying annotated graphs for analyses. highlight this application by annotating DNA sequences significant associations tetracycline macrolide resistance Streptococcus pneumoniae , identifying key determinants that were missed when only reference genome. novel analysis tool applications evolution epidemiology.

Язык: Английский

Likelihood-Free Inference by Ratio Estimation DOI Open Access
Owen Thomas, Ritabrata Dutta, Jukka Corander

и другие.

Bayesian Analysis, Год журнала: 2020, Номер 17(1)

Опубликована: Сен. 12, 2020

We consider the problem of parametric statistical inference when likelihood computations are prohibitively expensive but sampling from model is possible. Several so-called likelihood-free methods have been developed to perform in absence a function. The popular synthetic approach infers parameters by modelling summary statistics data Gaussian probability distribution. In another called approximate Bayesian computation, performed identifying parameter values for which simulated close those observed data. Synthetic easier use as no measure “closeness” required Gaussianity assumption often limiting. Moreover, both approaches require judiciously chosen statistics. here present an alternative that easy not restricted its assumptions, and that, natural way, enables automatic selection relevant statistic large set candidates. basic idea frame estimating posterior ratio between generating distribution marginal This can be solved logistic regression, including regularising penalty terms task. illustrate general theory on canonical examples employ it challenging stochastic nonlinear dynamical systems high-dimensional

Язык: Английский

Процитировано

72
Mechanisms That Shape Microbial Pangenomes DOI
Maria Rosa Domingo-Sananes,

James O. McInerney

Trends in Microbiology, Год журнала: 2021, Номер 29(6), С. 493 - 503

Опубликована: Янв. 9, 2021

Язык: Английский

Процитировано

58
Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study DOI Creative Commons
Stephanie W. Lo, Kate C. Mellor, Robert Cohen

и другие.

The Lancet Microbe, Год журнала: 2022, Номер 3(10), С. e735 - e743

Опубликована: Авг. 16, 2022

Язык: Английский

Процитировано

58
The potential of genomics for infectious disease forecasting DOI Open Access
Jessica E. Stockdale, Pengyu Liu, Caroline Colijn

и другие.

Nature Microbiology, Год журнала: 2022, Номер 7(11), С. 1736 - 1743

Опубликована: Окт. 20, 2022

Язык: Английский

Процитировано

49
Pneumococcal within-host diversity during colonization, transmission and treatment DOI Creative Commons
Gerry Tonkin‐Hill, Clare Ling, Chrispin Chaguza

и другие.

Nature Microbiology, Год журнала: 2022, Номер 7(11), С. 1791 - 1804

Опубликована: Окт. 10, 2022

Abstract Characterizing the genetic diversity of pathogens within host promises to greatly improve surveillance and reconstruction transmission chains. For bacteria, it also informs our understanding inter-strain competition how this shapes distribution resistant sensitive bacteria. Here we study Streptococcus pneumoniae 468 infants 145 their mothers by deep sequencing whole pneumococcal populations from 3,761 longitudinal nasopharyngeal samples. We demonstrate that has unsurpassed sensitivity for detecting multiple colonization, doubling rate at which highly invasive serotype 1 bacteria were detected in carriage compared with gold-standard methods. The greater resolution identified an elevated children first year child’s life. Comprehensive treatment data demonstrated risk both acquisition persistent colonization a multidrug-resistant bacterium following antimicrobial treatment. Some alleles enriched after treatment, suggesting they aided persistence, but generally purifying selection dominated within-host evolution. Rates co-colonization imply absence susceptible lineages outcompeted host. These results many benefits genomic bacterial pathogens.

Язык: Английский

Процитировано

45
Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis DOI
Noémie Lefrancq, Valérie Bouchez, Nadia Fernandes

и другие.

Science Translational Medicine, Год журнала: 2022, Номер 14(642)

Опубликована: Апрель 27, 2022

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries show that, on average, there 28.1 transmission chains circulating within a subnational region, the number strongly associated host population size. It took 5 10 years for B. be homogeneously distributed throughout Europe, same time frame required United States. Increased fitness pertactin-deficient after implementation acellular vaccines, but reduced otherwise, can explain long-term genotype dynamics. These findings highlight role vaccine policy shifting local pathogen that is responsible 160,000 deaths annually.

Язык: Английский

Процитировано

41
On the evolutionary ecology of multidrug resistance in bacteria DOI Creative Commons
Sonja Lehtinen, François Blanquart, Marc Lipsitch

и другие.

PLoS Pathogens, Год журнала: 2019, Номер 15(5), С. e1007763 - e1007763

Опубликована: Май 13, 2019

Resistance against different antibiotics appears on the same bacterial strains more often than expected by chance, leading to high frequencies of multidrug resistance. There are multiple explanations for this observation, but these tend be specific subsets and/or species, whereas trend is pervasive. Here, we consider question in terms strain ecology: explaining why resistance seen requires an understanding competition between with profiles. This work builds models originally proposed explain another aspect competition: stable coexistence antibiotic sensitivity and observed a number species. We first identify partial structural similarity models: either or host population structure stratifies pathogen into evolutionarily independent sub-populations introduces variation fitness effect sub-populations, thus creating niches then generalise unified underlying model show that predict levels association drugs frequencies. test predictions from six datasets find them qualitatively consistent trends. The higher interpreted as evidence out-competing lower multiplicity. Our provides alternative explanation compatible long-term stability

Язык: Английский

Процитировано

74
Resistance mechanisms and population structure of highly drug resistant Klebsiella in Pakistan during the introduction of the carbapenemase NDM-1 DOI Creative Commons
Eva Heinz, Hasan Ejaz, Josefin Bartholdson Scott

и другие.

Scientific Reports, Год журнала: 2019, Номер 9(1)

Опубликована: Фев. 20, 2019

Abstract Klebsiella pneumoniae is a major threat to public health with the emergence of isolates resistant most, if not all, useful antibiotics. We present an in-depth analysis 178 extended-spectrum beta-lactamase (ESBL)-producing K. collected from patients resident in region Pakistan, during period 2010–2012, when now globally-distributed carbapenemase bla -NDM-1 was being acquired by . observed two dominant lineages, but neither overall resistance profile nor virulence-associated factors, explain their evolutionary success. Phenotypic shows few differences between acquisition genes and phenotypic profile, including beta-lactam antibiotics that were used treat ESBL-positive strains. Resistance against these drugs could be explained inhibitor-resistant enzymes, carbapenemases or ampC type beta-lactamases, at least one which detected all relevant strains analysed. Complete genomes for six selected are reported, provide detailed insights into mobile elements initial spread NDM-1. The unexplained success some lineages within this pool highly strains, discontinuity genotype macro level, indicate intrinsic mechanisms contribute competitive advantage and/or resistance.

Язык: Английский

Процитировано

60
Designing ecologically optimized pneumococcal vaccines using population genomics DOI
Caroline Colijn, Jukka Corander, Nicholas J. Croucher

и другие.

Nature Microbiology, Год журнала: 2020, Номер 5(3), С. 473 - 485

Опубликована: Фев. 3, 2020

Язык: Английский

Процитировано

57
Geographical migration and fitness dynamics of Streptococcus pneumoniae DOI Creative Commons
Sophie Belman, Noémie Lefrancq, Susan Nzenze

и другие.

Nature, Год журнала: 2024, Номер 631(8020), С. 386 - 392

Опубликована: Июль 3, 2024

Abstract Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location 1,2 . The extent mechanisms spread vaccine-driven changes fitness antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa ( n = 6,910, collected 2000 to 2014), we developed models reconstruct spread, pairing detailed human mobility data genomic data. Separately, estimated the population-level strains that are included (vaccine type (VT)) not (non-vaccine (NVT)) pneumococcal conjugate vaccines, first implemented 2009. Differences strain between those resistant penicillin were also evaluated. We found pneumococci only become homogenously mixed across after 50 years transmission, with slow driven by focal nature mobility. Furthermore, following vaccine implementation, relative NVT compared VT increased (relative risk 1.68; 95% confidence interval 1.59–1.77), an increasing proportion these becoming penicillin. Our findings point highly entrenched, transmission indicate initial vaccine-linked decreases may be transient.

Язык: Английский

Процитировано

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