Genomic Epidemiology of Tuberculosis

Comas, Iñaki

doi:10.1007/978-3-319-64371-7_4

Cited by 20 publications

(20 citation statements)

References 70 publications

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“…Whole-genome sequencing (WGS) has transformed the way we analyze transmission of tuberculosis (TB) (Nikolayevskyy et al, 2016 ; Comas, 2017 ; Satta et al, 2017 ). Identification of transmission clusters is currently based on determination of the magnitude of genomic diversity among the isolates in a population.…”

Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts

et al. 2018

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Background: Mycobacterium tuberculosis (MTB) has limited ability to acquire variability. Analysis of its microevolution might help us to evaluate the pathways followed to acquire greater infective success. Whole-genome sequencing (WGS) in the analysis of the transmission of MTB has elucidated the magnitude of variability in MTB. Analysis of transmission currently depends on the identification of clusters, according to the threshold of variability (<5 SNPs) between isolates.Objective: We evaluated whether the acquisition of variability in MTB, was more frequent in situations which could favor it, namely intrapatient, prolonged infections or reactivations and interpatient transmissions involving multiple sequential hosts.Methods: We used WGS to analyze the accumulation of variability in sequential isolates from prolonged infections or translations from latency to reactivation. We then measured microevolution in transmission clusters with prolonged transmission time, high number of involved cases, simultaneous involvement of latency and active transmission.Results: Intrapatient and interpatient acquisition of variability was limited, within the ranges expected according to the thresholds of variability proposed, even though bursts of variability were observed.Conclusions: The thresholds of variability proposed for MTB seem to be valid in most circumstances, including those theoretically favoring acquisition of variability. Our data point to multifactorial modulation of microevolution, although further studies are necessary to elucidate the factors underlying this modulation.

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Section: Introductionmentioning

confidence: 99%

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts

et al. 2018

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“… 2015 ). However, even WGS does not detect all genetic variants that exist at very low frequencies (Comas 2017 ; Meehan et al . 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…The advent of DNA sequencing technologies, including NGS and WGS in particular, has revolutionized our ability to study the genetic diversity in the MTBC. Methodological aspects, advances and limitations in using NGS to study the MTBC were recently reviewed in (Comas 2017 ) and (Meehan et al . 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis

Castro

Borrell

Gagneux

2020

FEMS Microbiology Reviews

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Tuberculosis (TB) has been responsible for the greatest number of human deaths due to an infectious disease in general, and due to antimicrobial resistance (AMR) in particular. The etiological agents of human TB are a closely-related group of human-adapted bacteria that belong to the Mycobacterium tuberculosis complex (MTBC). Understanding how MTBC populations evolve within-host may allow for improved TB treatment and control strategies. In this review, we highlight recent works that have shed light on how AMR evolves in MTBC populations within individual patients. We discuss the role of heteroresistance in AMR evolution, and review the bacterial, patient and environmental factors that likely modulate the magnitude of heteroresistance within-host. We further highlight recent works on the dynamics of MTBC genetic diversity within-host, and discuss how spatial substructures in patients’ lungs, spatiotemporal heterogeneity in antimicrobial concentrations and phenotypic drug tolerance likely modulates the dynamics of MTBC genetic diversity in patients during treatment. We note the general characteristics that are shared between how the MTBC and other bacterial pathogens evolve in humans, and highlight the characteristics unique to the MTBC.

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“…TB research focused on imaging or genomic data analysis has recently achieved significant success [12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24]; however, there are still few investigations that encompass clinical, socioeconomic, image, and genomic data. Most TB databases and resources are domain specific, including ReSeqTB [25], PATRIC [26, 27], TB DB [28], ChestX-ray8: hospital-scale chest X-ray database [29] and others.…”

Section: Introductionmentioning

confidence: 99%

TB DEPOT (Data Exploration Portal): A multi-domain tuberculosis data analysis resource

et al. 2019

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The NIAID TB Portals Program (TBPP) established a unique and growing database repository of socioeconomic, geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis (DR-TB). Currently, there are 2,428 total cases from nine country sites (Azerbaijan, Belarus, Moldova, Georgia, Romania, China, India, Kazakhstan, and South Africa), 1,611 (66%) of which are multidrug- or extensively-drug resistant and 1,185 (49%), 863 (36%), and 952 (39%) of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. We introduce the Data Exploration Portal (TB DEPOT, https://depot.tbportals.niaid.nih.gov ) to visualize and analyze these multi-domain data. The TB DEPOT leverages the TBPP integration of clinical, socioeconomic, genomic, and imaging data into standardized formats and enables user-driven, repeatable, and reproducible analyses. It furthers the TBPP goals to provide a web-enabled analytics platform to countries with a high burden of multidrug-resistant TB (MDR-TB) but limited IT resources and inaccessible data, and enables the reusability of data, in conformity with the NIH’s Findable, Accessible, Interoperable, and Reusable (FAIR) principles. TB DEPOT provides access to “analysis-ready” data and the ability to generate and test complex clinically-oriented hypotheses instantaneously with minimal statistical background and data processing skills. TB DEPOT is also promising for enhancing medical training and furnishing well annotated, hard to find, MDR-TB patient cases. TB DEPOT, as part of TBPP, further fosters collaborative research efforts to better understand drug-resistant tuberculosis and aid in the development of novel diagnostics and personalized treatment regimens.

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Genomic Epidemiology of Tuberculosis

Cited by 20 publications

References 70 publications

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts

Mycobacterium tuberculosis Acquires Limited Genetic Diversity in Prolonged Infections, Reactivations and Transmissions Involving Multiple Hosts

The within-host evolution of antimicrobial resistance in Mycobacterium tuberculosis

TB DEPOT (Data Exploration Portal): A multi-domain tuberculosis data analysis resource

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