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| 2. |
- Ezewudo, M, et al.
(författare)
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Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 15382-
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Tidskriftsartikel (refereegranskat)abstract
- Drug-resistant tuberculosis poses a persistent public health threat. The ReSeqTB platform is a collaborative, curated knowledgebase, designed to standardize and aggregate global Mycobacterium tuberculosis complex (MTBC) variant data from whole genome sequencing (WGS) with phenotypic drug susceptibility testing (DST) and clinical data. We developed a unified analysis variant pipeline (UVP) (https://github.com/CPTR-ReSeqTB/UVP) to identify variants and assign lineage from MTBC sequence data. Stringent thresholds and quality control measures were incorporated in this open source tool. The pipeline was validated using a well-characterized dataset of 90 diverse MTBC isolates with conventional DST and DNA Sanger sequencing data. The UVP exhibited 98.9% agreement with the variants identified using Sanger sequencing and was 100% concordant with conventional methods of assigning lineage. We analyzed 4636 publicly available MTBC isolates in the ReSeqTB platform representing all seven major MTBC lineages. The variants detected have an above 94% accuracy of predicting drug based on the accompanying DST results in the platform. The aggregation of variants over time in the platform will establish confidence-graded mutations statistically associated with phenotypic drug resistance. These tools serve as critical reference standards for future molecular diagnostic assay developers, researchers, public health agencies and clinicians working towards the control of drug-resistant tuberculosis.
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| 3. |
- Miotto, P, et al.
(författare)
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A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
- 2017
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 50:6
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Tidskriftsartikel (refereegranskat)abstract
- A clear understanding of the genetic basis of antibiotic resistance inMycobacterium tuberculosisis required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype–phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6–90.9%), while for isoniazid it was 78.2% (77.4–79.0%) and their specificities were 96.3% (95.7–96.8%) and 94.4% (93.1–95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1–70.6%) for capreomycin to 88.2% (85.1–90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1–92.5%) for moxifloxacin to 99.5% (99.0–99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors ofM. tuberculosisdrug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.
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| 4. |
- Vandaele, Ann Carine, et al.
(författare)
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Martian dust storm impact on atmospheric H2O and D/H observed by ExoMars Trace Gas Orbiter
- 2019
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Ingår i: Nature. - : Springer. - 1476-4687 .- 1476-4687 .- 0028-0836. ; 568:7753, s. 521-525
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Global dust storms on Mars are rare1,2 but can affect the Martian atmosphere for several months. They can cause changes in atmospheric dynamics and inflation of the atmosphere3, primarily owing to solar heating of the dust3. In turn, changes in atmospheric dynamics can affect the distribution of atmospheric water vapour, with potential implications for the atmospheric photochemistry and climate on Mars4. Recent observations of the water vapour abundance in the Martian atmosphere during dust storm conditions revealed a high-altitude increase in atmospheric water vapour that was more pronounced at high northern latitudes5,6, as well as a decrease in the water column at low latitudes7,8. Here we present concurrent, high-resolution measurements of dust, water and semiheavy water (HDO) at the onset of a global dust storm, obtained by the NOMAD and ACS instruments onboard the ExoMars Trace Gas Orbiter. We report the vertical distribution of the HDO/H2O ratio (D/H) from the planetary boundary layer up to an altitude of 80 kilometres. Our findings suggest that before the onset of the dust storm, HDO abundances were reduced to levels below detectability at altitudes above 40 kilometres. This decrease in HDO coincided with the presence of water-ice clouds. During the storm, an increase in the abundance of H2O and HDO was observed at altitudes between 40 and 80 kilometres. We propose that these increased abundances may be the result of warmer temperatures during the dust storm causing stronger atmospheric circulation and preventing ice cloud formation, which may confine water vapour to lower altitudes through gravitational fall and subsequent sublimation of ice crystals3. The observed changes in H2O and HDO abundance occurred within a few days during the development of the dust storm, suggesting a fast impact of dust storms on the Martian atmosphere.
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