Genomic Analysis and Comparison of Two Gonorrhea Outbreaks

ABSTRACT Gonorrhea is a sexually transmitted disease causing growing concern, with a substantial increase in reported incidence over the past few years in the United Kingdom and rising levels of resistance to a wide range of antibiotics. Understanding its epidemiology is therefore of major biomedical importance, not only on a population scale but also at the level of direct transmission. However, the molecular typing techniques traditionally used for gonorrhea infections do not provide sufficient resolution to investigate such fine-scale patterns. Here we sequenced the genomes of 237 isolates from two local collections of isolates from Sheffield and London, each of which was resolved into a single type using traditional methods. The two data sets were selected to have different epidemiological properties: the Sheffield data were collected over 6 years from a predominantly heterosexual population, whereas the London data were gathered within half a year and strongly associated with men who have sex with men. Based on contact tracing information between individuals in Sheffield, we found that transmission is associated with a median time to most recent common ancestor of 3.4 months, with an upper bound of 8 months, which we used as a criterion to identify likely transmission links in both data sets. In London, we found that transmission happened predominantly between individuals of similar age, sexual orientation, and location and also with the same HIV serostatus, which may reflect serosorting and associated risk behaviors. Comparison of the two data sets suggests that the London epidemic involved about ten times more cases than the Sheffield outbreak. IMPORTANCE The recent increases in gonorrhea incidence and antibiotic resistance are cause for public health concern. Successful intervention requires a better understanding of transmission patterns, which is not uncovered by traditional molecular epidemiology techniques. Here we studied two outbreaks that took place in Sheffield and London, United Kingdom. We show that whole-genome sequencing provides the resolution to investigate direct gonorrhea transmission between infected individuals. Combining genome sequencing with rich epidemiological information about infected individuals reveals the importance of several transmission routes and risk factors, which can be used to design better control measures.

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Whole-genome analysis-based phylogeographic investigation of Streptococcus pneumoniae serotype 19A sequence type 320 isolates in Japan.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01395-21 ◽

2021 ◽

Author(s):

Satoshi Nakano ◽

Takao Fujisawa ◽

Bin Chang ◽

Yutaka Ito ◽

Hideki Akeda ◽

...

Keyword(s):

Common Ancestor ◽

Sampling Bias ◽

Health Concern ◽

Recent Common Ancestor ◽

Whole Genome ◽

Whole Genome Analysis ◽

Identification Rate ◽

Most Recent Common Ancestor ◽

The Common ◽

The U.S

After the introduction of the seven-valent pneumococcal conjugate vaccine, the global spread of multidrug resistant serotype 19A-ST320 strains became a public health concern. In Japan, the main genotype of serotype 19A was ST3111, and the identification rate of ST320 was low. Although the isolates were sporadically detected in both adults and children, their origin remains unknown. Thus, by combining pneumococcal isolates collected in three nationwide pneumococcal surveillance studies conducted in Japan between 2008 and 2020, we analyzed 56 serotype 19A-ST320 isolates along with 931 global isolates, using whole-genome sequencing to uncover the transmission route of the globally distributed clone in Japan. The clone was frequently detected in Okinawa Prefecture, where the U.S. returned to Japan in 1972. Phylogenetic analysis demonstrated that the isolates from Japan were genetically related to those from the U.S.; therefore, the common ancestor may have originated in the U.S. In addition, Bayesian analysis suggested that the time to the most recent common ancestor of the isolates form Japan and the U.S. was approximately the 1990s to 2000, suggesting the possibility that the common ancestor could have already spread in the U.S. before the Taiwan 19F-14 isolate was first identified in a Taiwanese hospital in 1997. The phylogeographical analysis supported the transmission of the clone from the U.S. to Japan, but the analysis could be influenced by sampling bias. These results suggested the possibility that the serotype 19A-ST320 clone had already spread in the U.S. before being imported into Japan.

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Global transmission and evolutionary dynamics of the Chikungunya virus

Epidemiology and Infection ◽

10.1017/s0950268820000497 ◽

2020 ◽

Vol 148 ◽

Cited By ~ 1

Author(s):

F. Deeba ◽

M. S. H. Haider ◽

A. Ahmed ◽

A. Tazeen ◽

M. I. Faizan ◽

...

Keyword(s):

Selection Pressure ◽

Chikungunya Virus ◽

Evolutionary Dynamics ◽

Control Measures ◽

Recent Common Ancestor ◽

Viral Pathogen ◽

Evolutionary Pattern ◽

Genetic Characterisation ◽

Most Recent Common Ancestor ◽

E1 Protein

Abstract Chikungunya virus (CHIKV) is a re-emerging pathogen of global importance. We attempted to gain an insight into the organisation, distribution and mutational load of the virus strains reported from different parts of the world. We describe transmission dynamics and genetic characterisation of CHIKV across the globe during the last 65 years from 1952 to 2017. The evolutionary pattern of CHIKV was analysed using the E1 protein gene through phylogenetic, Bayesian and Network methods with a dataset of 265 sequences from various countries. The time to most recent common ancestor of the virus was estimated to be 491 years ago with an evolutionary rate of 2.78 × 10−4 substitutions/site/year. Genetic characterisation of CHIKV strains was carried out in terms of variable sites, selection pressure and epitope mapping. The neutral selection pressure on the E1 gene of the virus suggested a stochastic process of evolution. We identified six potential epitope peptides in the E1 protein showing substantial interaction with human MHC-I and MHC-II alleles. The present study augments global epidemiological and population dynamics of CHIKV warranting undertaking of appropriate control measures. The identification of epitopic peptides can be useful in the development of epitope-based vaccine strategies against this re-emerging viral pathogen.

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The Most Recent Common Ancestor of Modern Humans was Born in Eurasia

10.20944/preprints202012.0470.v1 ◽

2020 ◽

Author(s):

vicente cabrera

Keyword(s):

Human Evolution ◽

Genome Sequencing ◽

Common Ancestor ◽

Recent Common Ancestor ◽

Whole Genome ◽

African Origin ◽

Modern Humans ◽

Most Recent Common Ancestor ◽

History Of ◽

New Vision

Ancient DNA has given a new vision to the recent history of human evolution. However, by always relying on the information provided by whole genome sequencing, some relevant relationships between modern humans and its archaic relatives have been misinterpreted by hybridization and recombination causes. In contrast, the congruent phylogeny, obtained from non-recombinant uniparental markers, indicates that humans and Neanderthals are sister subspecies, and that the most recent common ancestor of modern humans was not of African origin but Eurasian.

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Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation

Journal of Clinical Microbiology ◽

10.1128/jcm.00363-17 ◽

2017 ◽

Vol 55 (7) ◽

pp. 2188-2197 ◽

Cited By ~ 17

Author(s):

N. C. Gordon ◽

B. Pichon ◽

T. Golubchik ◽

D. J. Wilson ◽

J. Paul ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Recent Common Ancestor ◽

Whole Genome ◽

Epidemiological Evidence ◽

Host Diversity ◽

Most Recent Common Ancestor ◽

Highest Posterior Density

ABSTRACTWhole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, forStaphylococcus aureus, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (P= 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (P< 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.

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Revealing COVID-19 Transmission by SARS-CoV-2 Genome Sequencing and Agent Based Modelling

10.1101/2020.04.19.048751 ◽

2020 ◽

Cited By ~ 22

Author(s):

Rebecca J Rockett ◽

Alicia Arnott ◽

Connie Lam ◽

Rosemarie Sadsad ◽

Verlaine Timms ◽

...

Keyword(s):

Public Health ◽

Genome Sequencing ◽

New South ◽

Control Measures ◽

Health Concern ◽

Public Health Action ◽

Agent Based ◽

South Wales ◽

Health Action ◽

Community Transmission

ABSTRACTCommunity transmission of the new coronavirus SARS-CoV-2 is a major public health concern that remains difficult to assess. We present a genomic survey of SARS-CoV-2 from a during the first 10 weeks of COVID-19 activity in New South Wales, Australia. Transmission events were monitored prospectively during the critical period of implementation of national control measures. SARS-CoV-2 genomes were sequenced from 209 patients diagnosed with COVID-19 infection between January and March 2020. Only a quarter of cases appeared to be locally acquired and genomic-based estimates of local transmission rates were concordant with predictions from a computational agent-based model. This convergent assessment indicates that genome sequencing provides key information to inform public health action and has improved our understanding of the COVID-19 evolution from outbreak to epidemic.

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Frequentist Estimation of Coalescence Times From Nucleotide Sequence Data Using a Tree-Based Partition

Genetics ◽

10.1093/genetics/161.1.447 ◽

2002 ◽

Vol 161 (1) ◽

pp. 447-459 ◽

Cited By ~ 5

Author(s):

Hua Tang ◽

David O Siegmund ◽

Peidong Shen ◽

Peter J Oefner ◽

Marcus W Feldman

Keyword(s):

Dna Sequences ◽

Sequence Data ◽

Recent Common Ancestor ◽

Point Estimate ◽

Nucleotide Sequence Data ◽

Most Recent Common Ancestor ◽

Y Chromosomes ◽

Wide Range ◽

Nominal Coverage ◽

Biased Estimates

AbstractThis article proposes a method of estimating the time to the most recent common ancestor (TMRCA) of a sample of DNA sequences. The method is based on the molecular clock hypothesis, but avoids assumptions about population structure. Simulations show that in a wide range of situations, the point estimate has small bias and the confidence interval has at least the nominal coverage probability. We discuss conditions that can lead to biased estimates. Performance of this estimator is compared with existing methods based on the coalescence theory. The method is applied to sequences of Y chromosomes and mtDNAs to estimate the coalescent times of human male and female populations.

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Solving the Fisher-Wright and coalescence problems with a discrete Markov chain analysis

Advances in Applied Probability ◽

10.1239/aap/1103662962 ◽

2004 ◽

Vol 36 (4) ◽

pp. 1175-1197 ◽

Cited By ~ 2

Author(s):

Samuel R. Buss ◽

Peter Clote

Keyword(s):

Markov Chain ◽

Recent Common Ancestor ◽

Extinction Time ◽

Markov Chain Analysis ◽

Expected Time ◽

Most Recent Common Ancestor ◽

Chain Analysis ◽

Wide Range ◽

Mean Time ◽

Discrete Markov Chain

We develop a new, self-contained proof that the expected number of generations required for gene allele fixation or extinction in a population of size n is O(n) under general assumptions. The proof relies on a discrete Markov chain analysis. We further develop an algorithm to compute expected fixation or extinction time to any desired precision. Our proofs establish O(nH(p)) as the expected time for gene allele fixation or extinction for the Fisher-Wright problem, where the gene occurs with initial frequency p and H(p) is the entropy function. Under a weaker hypothesis on the variance, the expected time is O(n(p(1-p))1/2) for fixation or extinction. Thus, the expected-time bound of O(n) for fixation or extinction holds in a wide range of situations. In the multi-allele case, the expected time for allele fixation or extinction in a population of size n with n distinct alleles is shown to be O(n). From this, a new proof is given of a coalescence theorem about the mean time to the most recent common ancestor (MRCA), which applies to a broad range of reproduction models satisfying our mean and weak variation conditions.

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Acinetobacter spp in a Third World Country with Socio-economic and Immigrants Challenges

The Journal of Infection in Developing Countries ◽

10.3855/jidc.11341 ◽

2019 ◽

Vol 13 (11) ◽

pp. 948-955

Author(s):

Iman Dandachi ◽

Eid Azar ◽

Ramzi Hamouch ◽

Peter Maliha ◽

Samah Abdallah ◽

...

Keyword(s):

Human Infection ◽

Control Measures ◽

Health Concern ◽

Acinetobacter Species ◽

Infection Control Measures ◽

Third World Country ◽

Wide Range ◽

Potential Pathogen ◽

Acinetobacter Spp ◽

The One

Introduction: In the last decade, Acinetobacter species have taken a major public health concern. This is mainly due the increased resistance to a wide range of antibiotics causing treatment challenges. In view of the constant population mobilization and the economic crisis that Lebanon is currently facing, it becomes a necessity to re-evaluate the real threat of Acinetobacter spp and its implication in the one health. Methodology: This review was conducted through the analysis of 45 research papers and reports pertaining to Acinetobacter spp performed in Lebanon. More than 82% of the papers consulted were published in international journals and more than 70 percent of them had received impact factor. Results: An in depth description of the involvement of this organism in human infection and its role as potential pathogen or simple colonizer was performed. In addition, the different aspects of resistance, mostly to carbapenems and colistin was studied and summarized. While in animals and environment, susceptible strains were mostly isolated, OXA-23/OXA-24 were predominant in humans. Recently, NDM-1 producing Acinetobacter spp was detected in a Syrian refugee which then was reported in Lebanese patients. The bacterial identification procedures are non-systematic and not always reliable in the Lebanese studies presenting sometimes discrepancies an inconsistency. Conclusion: Acinetobacter is commonly isolated Lebanon. In view of the spread of resistance among these isolated and their dissemination, Infection control measures attempting to control the spread of this genus in and outside hospitals are lacking and thus require more attention and stewardship activities.

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Population divergence time estimation using individual lineage label switching

10.1101/587832 ◽

2019 ◽

Author(s):

Peter Beerli ◽

Haleh Ashki ◽

Somayeh Mashayekhi ◽

Michal Palczewski

Keyword(s):

Divergence Time ◽

Time Estimation ◽

Random Variable ◽

Recent Common Ancestor ◽

Population Divergence ◽

Inference Method ◽

Divergence Time Estimation ◽

Most Recent Common Ancestor ◽

Wide Range ◽

Truncated Normal

AbstractDivergence time estimation from multilocus genetic data has become common in population genetics and phylogenetics. We present a new Bayes inference method that treats the divergence time as a random variable. The divergence time is calculated from an assembly of splitting events on individual lineages in a genealogy. The waiting time for such a splitting event is drawn from a hazard function of the truncated normal distribution. This allows easy integration into the standard coalescence framework used in programs such as MIGRATE. We explore the accuracy of the new inference method with simulated population splittings over a wide range of divergence time values and with a dataset of the Zika virus; the geographic analyses of the expansion of the pathogen follows a trajectory from Africa to Asia to America, corroborating analyses based only on the dates of incidences. Evaluations of simple divergence models show high accuracy, whereas the accuracy of the results of isolation with migration (IM) models depend on the magnitude of the immigration rate and potentially on the number of samples. High immigration rates lead to a time of the most recent common ancestor of the sample that predates the divergence time, thus loses any potential signal of the divergence event in the sample data. This reduced accuracy with high immigration rates is problematic for all IM methods, including ours.

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An accurate genetic clock

10.1101/019414 ◽

2015 ◽

Author(s):

David H Hamilton

Keyword(s):

Stochastic Process ◽

Kin Selection ◽

Common Ancestor ◽

Mutation Rates ◽

Recent Common Ancestor ◽

Molecular Clocks ◽

Most Recent Common Ancestor ◽

Wide Range ◽

Short And Long Term

Molecular clocks give ``Time to most recent common ancestor'' TMRCA} of genetic trees. By Watson-Galton most lineages terminate, with a few overrepresented singular lineages generated by W. Hamilton's ``kin selection''. Applying current methods to this non-uniform branching produces greatly exaggerated TMRCA. We introduce an inhomogenous stochastic process which detects singular lineages by asymmetries, whose reduction gives true TMRCA. This implies a new method for computing mutation rates. Despite low rates similar to mitosis data, reduction implies younger TMRCA, with smaller errors. We establish accuracy by a comparison across a wide range of time, indeed this is only clock giving consistent results for both short and long term times. In particular we show that the dominant European y-haplotypes R1a1a & R1b1a2, expand from c3700BC, not reaching Anatolia before c3300BC. While this contradicts current clocks which date R1b1a2 to either the Neolithic Near East$ or Paleo-Europe, our dates support recent genetic analysis of ancient skeletons by Reich.

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