scholarly journals Population structure, biogeography and transmissibility of Mycobacterium tuberculosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Luca Freschi ◽  
Roger Vargas ◽  
Ashaque Husain ◽  
S. M. Mostofa Kamal ◽  
Alena Skrahina ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Population Structure ◽  
Global Scale ◽  
Rapid Identification ◽  
Genomic Diversity ◽  
Terminal Branch ◽  
Nucleotide Substitutions ◽  
Central Asian ◽  
Depth Analysis ◽  
Branch Lengths

AbstractMycobacterium tuberculosis is a clonal pathogen proposed to have co-evolved with its human host for millennia, yet our understanding of its genomic diversity and biogeography remains incomplete. Here we use a combination of phylogenetics and dimensionality reduction to reevaluate the population structure of M. tuberculosis, providing an in-depth analysis of the ancient Indo-Oceanic Lineage 1 and the modern Central Asian Lineage 3, and expanding our understanding of Lineages 2 and 4. We assess sub-lineages using genomic sequences from 4939 pan-susceptible strains, and find 30 new genetically distinct clades that we validate in a dataset of 4645 independent isolates. We find a consistent geographically restricted or unrestricted pattern for 20 groups, including three groups of Lineage 1. The distribution of terminal branch lengths across the M. tuberculosis phylogeny supports the hypothesis of a higher transmissibility of Lineages 2 and 4, in comparison with Lineages 3 and 1, on a global scale. We define an expanded barcode of 95 single nucleotide substitutions that allows rapid identification of 69 M. tuberculosis sub-lineages and 26 additional internal groups. Our results paint a higher resolution picture of the M. tuberculosis phylogeny and biogeography.

scholarly journals Population structure, biogeography and transmissibility of Mycobacterium tuberculosis

2020 ◽  
Author(s):  
Luca Freschi ◽  
Roger Vargas ◽  
Ashek Hussain ◽  
S M Mostofa Kamal ◽  
Alena Skrahina ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Population Structure ◽  
Global Scale ◽  
Rapid Identification ◽  
Genomic Diversity ◽  
Terminal Branch ◽  
East African ◽  
Nucleotide Substitutions ◽  
Central Asian ◽  
Depth Analysis

AbstractMycobacterium tuberculosis is a clonal pathogen proposed to have co-evolved with its human host for millennia, yet our understanding of its genomic diversity and biogeography remains incomplete. Here we use a combination of phylogenetics and dimensionality reduction to reevaluate the population structure of M. tuberculosis, providing the first in-depth analysis of the ancient East African Indian Lineage 1 and the modern Central Asian Lineage 3 and expanding our understanding of Lineages 2 and 4. We assess sub-lineages using genomic sequences from 4,939 pan-susceptible strains and find 30 new genetically distinct clades that we validate in a dataset of 4,645 independent isolates. We characterize sub-lineage geographic distributions and demonstrate a consistent geographically restricted and unrestricted pattern for 20 groups, including three groups of Lineage 1. We assess the transmissibility of the four major lineages by examining the distribution of terminal branch lengths across the M. tuberculosis phylogeny and identify evidence supporting higher transmissibility in Lineages 2 and 4 than 3 and 1 on a global scale. We define a robust expanded barcode of 95 single nucleotide substitutions (SNS) that allows for the rapid identification of 69 Mtb sub-lineages and 26 additional internal groups. Our results paint a higher resolution picture of the Mtb phylogeny and biogeography.

scholarly journals Understanding drivers of phylogenetic clustering and terminal branch lengths distribution in epidemics of Mycobacterium tuberculosis

2022 ◽  
Author(s):  
Fabrizio Menardo
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Transmission Rate ◽  
Basic Reproductive Number ◽  
Infectious Period ◽  
Reproductive Number ◽  
Data Sets ◽  
Terminal Branch ◽  
Branch Lengths ◽  
Disease Epidemics ◽  
Epidemiological Characteristics

Detecting factors associated with transmission is important to understand disease epidemics, and to design effective public health measures. Clustering and terminal branch lengths (TBL) analyses are commonly applied to genomic data sets of Mycobacterium tuberculosis (MTB) to identify sub-populations with increased transmission. Here, I used a simulation-based approach to investigate what epidemiological processes influence the results of clustering and TBL analyses, and whether difference in transmission can be detected with these methods. I simulated MTB epidemics with different dynamics (latency, infectious period, transmission rate, basic reproductive number R0, sampling proportion, and molecular clock), and found that all these factors, except the length of the infectious period and R0, affect the results of clustering and TBL distributions. I show that standard interpretations of this type of analyses ignore two main caveats: 1) clustering results and TBL depend on many factors that have nothing to do with transmission, 2) clustering results and TBL do not tell anything about whether the epidemic is stable, growing, or shrinking. An important consequence is that the optimal SNP threshold for clustering depends on the epidemiological conditions, and that sub-populations with different epidemiological characteristics should not be analyzed with the same threshold. Finally, these results suggest that different clustering rates and TBL distributions, that are found consistently between different MTB lineages, are probably due to intrinsic bacterial factors, and do not indicate necessarily differences in transmission or evolutionary success.

scholarly journals Modern lineages of Mycobacterium tuberculosis were recently introduced in western India and demonstrate increased transmissibility

2022 ◽  
Author(s):  
Avika Dixit ◽  
Anju Kagal ◽  
Yasha Ektefaie ◽  
Luca Freschi ◽  
Rajesh Karyakarte ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Cohort Studies ◽  
Molecular Dating ◽  
Contact Tracing ◽  
Sputum Smear ◽  
Western India ◽  
Terminal Branch ◽  
Significant Difference ◽  
Branch Lengths ◽  
Ks Test

Background: Mycobacterium tuberculosis (Mtb) transmissibility may vary between lineages (or variants) and this may contribute to the slow decline of tuberculosis (TB) incidence. The objective of our study was to compare transmissibility across four major lineages (L1-4) of Mtb among participants from two cohort studies in Pune, India. Methods: We performed whole-genome sequencing (WGS) of Mtb sputum culture-positive isolates from participants in two prospective cohort studies of adults with pulmonary TB seeking care at public treatment centers in Pune, Maharashtra. We performed genotypic susceptibility prediction for both first- and second-line drugs using a previously validated random forest model. We used single nucleotide substitutions (SNS) and maximum likelihood estimation to build isolate phylogenies by lineage. We used Bayesian molecular dating to estimate ancestral node ages and compared tree characteristics using a two-sample Kolmogorov-Smirnov (KS) test. Results: Of the 642 isolates from distinct study participants that underwent WGS, 612 met sequence quality criteria. The median age of the 612 participants was 31 years (IQR 24.4-44.2), the majority were male (64.7%) and sputum smear-positive (83.3%), and 6.7% had co-infection with HIV. Most isolates belonged to L3 (44.6%). The majority (61.1%) of multidrug-resistant isolates (MDR, resistant to isoniazid and rifampin) belonged to L2 (P < 0.001 [Fisher's Exact]). There was no significant difference in host characteristics between participants infected with the four major lineages. In phylogenetic analysis, we measured shorter terminal branch lengths in the L2 tree compared to L1 and L3 trees indicating less time elapsing between transmission and sampling and higher transmissibility (median branch lengths: L2 - 3.3, L3 - 7.8, p <0.001). Branching times for L2 and L4 were more recent than L1 and L3 indicating recent introduction into the region (p < 0.01 [KS test]). Conclusion: Modern Mtb lineages (L2 and L4) were more recently introduced in western India, compared to older lineages (L1 and L3). L2 shows a higher frequency of drug-resistance and higher transmissibility. Our findings highlight the need for contact tracing around cases of TB due to L2, and heightened surveillance of TB antibiotic resistance in India.

scholarly journals Assessing genomic diversity and signatures of selection in Jiaxian Red cattle using whole-genome sequencing data

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoting Xia ◽  
Shunjin Zhang ◽  
Huaju Zhang ◽  
Zijing Zhang ◽  
Ningbo Chen ◽  
...  
Keyword(s):  
Population Structure ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Genomic Variation ◽  
Genomic Diversity ◽  
System Response ◽  
Whole Genome ◽  
Population Structure Analysis ◽  
Native Cattle ◽  
Genomic Regions

Abstract Background Native cattle breeds are an important source of genetic variation because they might carry alleles that enable them to adapt to local environment and tough feeding conditions. Jiaxian Red, a Chinese native cattle breed, is reported to have originated from crossbreeding between taurine and indicine cattle; their history as a draft and meat animal dates back at least 30 years. Using whole-genome sequencing (WGS) data of 30 animals from the core breeding farm, we investigated the genetic diversity, population structure and genomic regions under selection of Jiaxian Red cattle. Furthermore, we used 131 published genomes of world-wide cattle to characterize the genomic variation of Jiaxian Red cattle. Results The population structure analysis revealed that Jiaxian Red cattle harboured the ancestry with East Asian taurine (0.493), Chinese indicine (0.379), European taurine (0.095) and Indian indicine (0.033). Three methods (nucleotide diversity, linkage disequilibrium decay and runs of homozygosity) implied the relatively high genomic diversity in Jiaxian Red cattle. We used θπ, CLR, FST and XP-EHH methods to look for the candidate signatures of positive selection in Jiaxian Red cattle. A total number of 171 (θπ and CLR) and 17 (FST and XP-EHH) shared genes were identified using different detection strategies. Functional annotation analysis revealed that these genes are potentially responsible for growth and feed efficiency (CCSER1), meat quality traits (ROCK2, PPP1R12A, CYB5R4, EYA3, PHACTR1), fertility (RFX4, SRD5A2) and immune system response (SLAMF1, CD84 and SLAMF6). Conclusion We provide a comprehensive overview of sequence variations in Jiaxian Red cattle genomes. Selection signatures were detected in genomic regions that are possibly related to economically important traits in Jiaxian Red cattle. We observed a high level of genomic diversity and low inbreeding in Jiaxian Red cattle. These results provide a basis for further resource protection and breeding improvement of this breed.

scholarly journals Gastrointestinal carriage of Klebsiella pneumoniae in a general adult population in Norway: a cross-sectional study of risk factors and bacterial genomic diversity

2021 ◽  
Author(s):  
Niclas Raffelsberger ◽  
Marit Andrea Klokkhammer Hetland ◽  
Kristian Svendsen ◽  
Lars Småbrekke ◽  
Iren H. Löhr ◽  
...  
Keyword(s):  
Risk Factors ◽  
Population Structure ◽  
General Population ◽  
Klebsiella Pneumoniae ◽  
Representative Sample ◽  
Adult Population ◽  
Antibiotic Use ◽  
Genomic Diversity ◽  
Prescription Database ◽  
Hospitalised Patients

SummaryBackgroundKlebsiella pneumoniae is a leading public health threat due to its increasing prevalence of antibiotic resistance. Gastrointestinal carriage of K. pneumoniae is a risk factor for subsequent infections in hospitalised patients. We determined risk factors for gastrointestinal carriage and the genomic population structure of K. pneumoniae colonising humans in a representative sample of a general population.Methods2,975 individuals (54% women) ≥40y participating in the population-based Tromsø Study 7 (2015-2016) were included. Faecal samples were screened for K. pneumoniae which were characterised using whole-genome sequencing. Risk factors for carriage were analysed using data from the Norwegian Prescription Database and questionnaires, using multivariable logistic regression.FindingsPrevalence of K. pneumoniae gastrointestinal carriage was 16·3% (95% CI 15·0-17·7%) with no gender difference. Risk factors associated with carriage included age ≥60y, travel to Greece or Asia past 12 months (adjusted odds ratio 1·49, 95% CI 1·11-2·00), Crohn’s disease/ulcerative colitis (2·26, 1·20-4·27), use of protein pump inhibitors (1·62, 1·18-2·22) and non-steroidal anti-inflammatory drugs past six months (1·38, 1·04-1·84), and antibiotic use last month (1·73, 1·05-2·86). Prevalence was higher among those having used combinations of drug classes and decreased over time with respect to preceding antibiotic use. The K. pneumoniae population was diverse with 300 sequence types among 484 isolates distributed across four phylogroups. Among the isolates, 5·2% and 11·6% harboured acquired resistance and virulence factors, respectively.InterpretationIdentification of risk factors for gastrointestinal carriage in a representative sample of a general population allows for identification of individuals that may have a higher risk of extraintestinal infection during hospitalisation. The diverse population structure of K. pneumoniae carriage isolates reflects the ecologically adaptive capacity of the bacterium, and the low antibacterial consumption probably contributes to the low prevalence of resistance in clinical isolates in Norway.

scholarly journals Whole-genome SNP analysis elucidates the genetic population structure and diversity of Acrocomia species

2020 ◽  
Author(s):  
Brenda G. Díaz ◽  
Maria I. Zucchi ◽  
Alessandro. Alves-Pereira ◽  
Caléo P. de Almeida ◽  
Aline C. L. Moraes ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Population Structure ◽  
Genetic Structure ◽  
Genetic Relationships ◽  
Geographical Area ◽  
Taxonomic Classification ◽  
Genomic Diversity ◽  
Productive Capacity ◽  
Snp Analysis ◽  
Genetic Population

AbstractAcrocomia (Arecaceae) is a genus widely distributed in tropical and subtropical America that has been achieving economic interest due to the great potential of oil production of some of its species. In particular A. aculeata, due to its vocation to supply oil with the same productive capacity as the oil palm even in areas with water deficit. Although eight species are recognized in the genus, the taxonomic classification based on morphology and geographic distribution is still controversial. Knowledge about the genetic diversity and population structure of the species is limited, which has limited the understanding of the genetic relationships and the orientation of management, conservation, and genetic improvement activities of species of the genus. In the present study, we analyzed the genomic diversity and population structure of seven species of Acrocomia including 117 samples of A. aculeata covering a wide geographical area of occurrence, using single nucleotide Polymorphism (SNP) markers originated from Genotyping By Sequencing (GBS). The genetic structure of the Acrocomia species were partially congruent with the current taxonomic classification based on morphological characters, recovering the separation of the species A. aculeata, A. totai, A. crispa and A. intumescens as distinct taxonomic groups. However, the species A. media was attributed to the cluster of A. aculeata while A. hassleri and A. glauscescens were grouped together with A. totai. The species that showed the highest and lowest genetic diversity were A. totai and A. media, respectively. When analyzed separately, the species A. aculeata showed a strong genetic structure, forming two genetic groups, the first represented mainly by genotypes from Brazil and the second by accessions from Central and North American countries. Greater genetic diversity was found in Brazil when compared to the other countries. Our results on the genetic diversity of the genus are unprecedented, as is also establishes new insights on the genomic relationships between Acrocomia species. It is also the first study to provide a more global view of the genomic diversity of A. aculeata. We also highlight the applicability of genomic data as a reference for future studies on genetic diversity, taxonomy, evolution and phylogeny of the Acrocomia genus, as well as to support strategies for the conservation, exploration and breeding of Acrocomia species and in particular A. aculeata.

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