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630 results for “Mycobacterium tuberculosis”
The within-host population dynamics of Mycobacterium tuberculosis vary with treatment efficacy.
<p>Data used for the publication of a paper entitled: <strong>The within-host population dynamics of <em>Mycobacterium tuberculosis</em> vary with treatment efficacy.</strong></p> <p>The data were derived from:</p> <p>1. the deep sequencing of serial sputum samples from 12 TB patients,</p> <p>2. the deep sequencing of liquid cultures derived from the expansion of individual colonies <em>in vitro</em>,</p> <p>3. <em>In </em><em>silico</em> simulations of DNA sequencing, populations and mutagenesis.</p> <p>The analytical scripts associated with the generation of the data can be found at:</p> <p>https://github.com/swisstph/TBRU_serialTB/</p> <p><strong>Paper Abstract:</strong></p> <p><strong>Background:</strong></p> <p>Combination therapy is one of the most effective tools for limiting the emergence of drug resistance. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We addressed this question by studying the population dynamics of <em>Mycobacterium tuberculosis</em> within tuberculosis patients undergoing treatment with different combinations of antibiotics.</p> <p><strong>Results:</strong></p> <p>By combining very deep whole genome sequencing (~1,000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy had a clear impact on the population dynamics: sufficient drug pressure bore a clear signature of purifying selection leading to apparent genetic stability. In contrast, <em>M. tuberculosis</em> populations subject to less drug pressure showed markedly different dynamics, including cases of acquisition of additional drug resistance.</p> <p><strong>Conclusions:</strong></p> <p>Our findings show that for a pathogen like <em>M. tuberculosis</em>, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.</p>
Whole-genome capture and sequencing of Mycobacterium tuberculosis directly from clinical samples - Design of RNA oligonucleotide baits for Agilent Technologies' SureSelect target enrichment
<p>This dataset comprises the sequence of <strong>44 278 RNA oligonucleotide "baits" (120 bp each) </strong>designed to perform <strong>whole-genome capture and sequencing of <em>Mycobacterium tuberculosis</em> directly from clinical samples</strong> (DNA) using Agilent Technologies’ SureSelect target enrichment system following the Illumina paired-end multiplexed sequencing library protocol. </p> <p>RNA oligonucleotide “baits” were designed to span the ∼4.5 Mb of the <em>M. tuberculosis</em> genome. In brief, the reference genome sequence of the MTBC H37Rv strain (Genbank #AL123456) was <em>in silico</em> fragmented into 120 bp sequences twice, to ensure an overlap of 60 bp between sequences. Due to their rich GC content, which could interfere with DNA capture, all MTBC genes of the PE, PPE and PE-PGRS family were also independently fragmented into 120 bp sequences, in order to increase capture sensitivity. All resulting sequences were BLASTn searched against the Human Genomic + Transcript database to excluded homologous sequences to the human genome. Overall, a total of 42,278 RNA probes were generated and this custom bait library was then uploaded to the SureDesign software (https://earray.chem.agilent.com/suredesign) and synthesized by Agilent Technologies. During synthesis, the 2198 sequences complementary to the PE, PPE and PE-PGRS family were unbalanced 8:1 to potentiate capture.</p> <p>More details can be found in the following publication:</p> <p>- Macedo, R., Isidro, J., Ferreira, R., Pinto, M., Borges, V., Duarte, S., Vieira, L., & Gomes, J. P. (2023). Molecular Capture of <em>Mycobacterium tuberculosis</em> Genomes Directly from Clinical Samples: A Potential Backup Approach for Epidemiological and Drug Susceptibility Inferences. <em>International journal of molecular sciences</em>, <em>24</em>(3), 2912. https://doi.org/10.3390/ijms24032912</p>
Multiple Sequence Alignment of a diverse dataset with 1788 Mycobacterium tuberculosis isolates
<p><strong>Multiple Sequence Alignment of a diverse dataset with 1788 <em>Mycobacterium tuberculosis</em> isolates used for <a href="https://github.com/insapathogenomics/ReporTree">ReporTree</a> benchmarking</strong></p> <p>The dataset comprises whole-genome sequence data published by <a href="https://doi.org/10.1016/S1473-3099(15)00062-6">Walker et al. 2015</a>. For the multiple sequence analysis, we proceeded as follows:</p> <ol> <li>Reads were downloaded from ENA BioProject <a href="https://www.ncbi.nlm.nih.gov/bioproject/PRJNA282721">PRJNA282721</a> (accessed on March 16<sup>th</sup>, 2023) and trimmed using Trimmomatic (<a href="https://pubmed.ncbi.nlm.nih.gov/24695404/">Bolger et al., 2014</a>) with <a href="https://github.com/B-UMMI/INNUca">INNUca</a> default settings;</li> <li>Quality-processed reads were individually mapped against the H37Rv reference genome (Genbank accession: <a href="https://www.ncbi.nlm.nih.gov/nuccore/NC_000962.3/">NC_000962.3</a>) using <a href="https://github.com/tseemann/snippy">Snippy</a> v4.5.1 and SNP-calling was performed on variant sites with the following criteria: a minimum proportion of reads differing from the reference of 70%, a minimum mapping quality of 30 and a minimum coverage for SNP calling of 10;</li> <li>A full alignment was extracted using Snippy’s core module (snippy-core), with masking of SNPs falling within known <em>M. tuberculosis</em> genomic regions with high GC content, repetitive elements and resistance-associated positions (corresponding to ~8% of the genome), as previously described for surveillance purposes (<a href="https://pubmed.ncbi.nlm.nih.gov/30948181/">Macedo et al., 2019</a>);</li> <li><em>M. tuberculosis </em>lineages were determined using tb-profiler v4.4.1 (<a href="https://pubmed.ncbi.nlm.nih.gov/31234910/">Phelan et al., 2019</a>), with samples from the <em>M. tuberculosis</em> complex other than <em>M. tuberculosis</em>, representing a mix of multiple lineages, or with less than 95% of mapped positions in the reference, being excluded;</li> <li>A filtered alignment comprising the maximum number of informative sites (88,562 nucleotide sites with at least one mutation in a given sequence) was extracted from the full alignment using the alignment_processing.py v1.1.0 (default settings) of <a href="https://github.com/insapathogenomics/ReporTree">ReporTree</a>, and then used as input for the benchmarking.</li> </ol> <p>In this repository, we provide two alignment files:</p> <ul> <li>Core_MTB_1787_strs.full.aln: this corresponds to the full multiple sequence alignment comprising 1787 samples and the reference (corresponding to the point 4 of the methodology).</li> <li>MTb_original_align_profile.fasta: this corresponds to the multiple sequence alignment comprising 1787 samples and the reference and only presenting the alignment informative sites (corresponding to the point 5 of the methodology)</li> </ul>
X-ray diffraction images for the H145E mutant of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis.
<p>X-ray diffraction images of the H145E mutant (prefixed h145e) which were collected in October 1995 using a graphite-monochromated copper K-alpha rotating anode source (wavelength 1.5418 Å) with a Marresearch 90 cm image plate detector at a distance of 120 mm from the crystal. The data were collected at room temperature in two passes, each consisting of 100 one degree rotations of the crystal. Each image had an exposure time of 20 minutes. The crystal was rotated in the capillary tube prior to collection of the second pass in order to record the 'blind' region of the diffraction pattern and this set of images is prefixed h145eb. </p>
X-ray diffraction images for the H145Q mutant of the iron-dependent superoxide dismutase from Mycobacterium tuberculosis.
<p>X-ray diffraction images collected from one crystal at room temperature using a rotating anode copper source (wavelength 1.5418 Å) and a 30 cm Marresearch image plate detector. The crystal-to-detector distance was 150 mm and a 90 mm image plate scan radius was used. Each of the 60 images had an exposure time of 20 minutes and corresponds to a 3 degree phi-rotation of the crystal. Diffraction extends to about 3.3 Å resolution. </p>
User Guide – Dashboard on Zoonotic tuberculosis: Mycobacterium
<p>User Guide – Dashboard on Zoonotic tuberculosis focusing on Mycobacterium bovis and M. caprae</p>
Dataset from Remote analysis of Sputum Smears for Mycobacterium Tuberculosis Quantification using Digital Crowdsourcing
<p>Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent. Although the development and roll out of Xpert MTB/RIF has recently become a major breakthrough in the field of TB diagnosis, smear microscopy remains the most widely used method for TB diagnosis, especially in low- and middle-income countries.</p> <p>This is a minimal dataset to reproduce our research that tests the feasibility of a crowdsourced approach to tuberculosis image analysis. In particular, we investigated whether anonymous volunteers with no prior experience would be able to count acid-fast bacilli in digitized images of sputum smears by playing an online game. Following this approach 1790 people identified the acid-fast bacilli present in 60 digitized images, the best overall performance was obtained with a specific number of combined analysis from different players and the performance was evaluated with the F1 score, sensitivity and positive predictive value, reaching values of 0.933, 0.968 and 0.91, respectively.</p> <p>The dataset includes 24 digitized images of sputum smears and the corresponding gameplays clicks. </p>
Flexible nitrogen utilisation by the metabolic generalist pathogen Mycobacterium tuberculosis
<p>Data on uptake and metabolism of all 20 amino acids by Mycobacterium tuberculosis H37Rv (20 amino acids uptake.zip), shown in Figure 2.</p> <p>Data on kinetics of labelling on 15N-Asp (15N Asp.zip), shown in Figure 4g and h.</p> <p>Data on kinetics of labelling on 15N2-Asn (15N Asn.zip), shown in Figure 4g and h.</p> <p>Data on kinetics of labelling on 15N-Glu (15N Glu.zip), shown in Figure 4g and h.</p> <p>Data on kinetics of labelling on 15N2-Gln (15N Gln.zip), shown in Figure 4g and h.</p> <p>Data on kinetics of labelling on 15N-NH4+ (15N NH4+.zip), shown in Figure 4g and h.</p> <p>Data on position specific labelling with Asn and Gln (PIL.zip), shown in Figure 4b to f.</p> <p>Data on co-metabolism of Glu/Gln and Asp/Asn (co-metabolism.zip), shown in Figure 5.</p>
Mycobacterium tuberculosis database
<p>This database contains the <em>M. tuberculosis</em> H37Rv reference genome (RefSeq accession GCF_000195955.2), plus 17 high-quality <em>M. tuberculosis</em> references from lineages 1-6 (from https://doi.org/10.1186/s13059-021-02474-0 - see mtb_gramtools_lineages.csv for the list of accessions).</p>
Data from: Pleomorphic effects of three small-molecule inhibitors on transcription elongation by <em>Mycobacterium tuberculosis</em> RNA polymerase
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Whole genome sequence data of Mycobacterium tuberculosis and Mycolicibacterium smegmatis mutants of the riboflavin biosynthetic pathway- Part 1
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Human memory CD4+ T cells recognize <em>Mycobacterium tuberculosis</em>-infected macrophages amid broader pathogen-specific responses
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Whole genome sequence data of Mycobacterium tuberculosis and Mycolicibacterium smegmatis mutants of the riboflavin biosynthetic pathway- Part 2
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GENOMIC INSIGHTS INTO THE GLOBAL EVOLUTION AND ANTIBIOTIC RESISTANCE OF THE MYCOBACTERIUM TUBERCULOSIS COMPLEX
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Genome of the inferred most recent common ancestor of the Mycobacterium tuberculosis complex
<p>Genome of the inferred most recent common ancestor of the <em>Mycobacterium tuberculosis</em> complex (MTBC) as described in <em>Human T cell epitopes of </em>Mycobacterium tuberculosis<em> are evolutionarily hyperconserved</em>. Comas et al 2010; Nature Genetics (doi:10.1038/ng.590).</p> <p>Mapping to the inferred MTBC ancestor instead of an extant, Lineage 4/LAM strain, allows to better distinguish between ancestral and derived mutations. This is exemplified by the number of single-nucleotide polymorphisms called for strains from different MTBC lineages (Figure 1).</p> <p>Figure 1 shows the number of fixed SNPs (fSNPs; allele frequency >= 90%), called for <em>Mycobacterium tuberculosis</em> isolates from different MTBC lineages when aligning to the reference strain H37Rv or to the MTBC ancestor. Each dot is an isolate. When aligning to the MTBC ancestor, some isolates appear as "outliers", with less fSNPs than the average. These are mixed infections.</p>
Drug sensitive and multidrug-resistant Mycobacterium tuberculosis genotypes from Bulgaria
<p>Dataset of drug sensitive and multidrug-resistant Mycobacteium tuberculosis spoligo- and MIRU-VNTR genotypes from Bulgaria collected between 2008 till 2019.</p>
Mycobacterium tuberculosis complex NGS made easy: data analysis step-by-step (datasets)
<p>Datasets used in the workshop "<em>Mycobacterium tuberculosis</em> complex NGS made easy: data analysis step-by-step". A capacity development initiative by TB-CAPT, PanACEA and Seq&Treat.</p>
Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis
<p>Datasets for the Figures 2 and S2 of the manuscript "Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis".</p> <p> </p> <p>The HTML files describe the analysis and the raw counts after nEMOTE-conv treatment.</p> <p>There are 5 files for each MMEMOTExx dataset:</p> <p>EmoteBarcodesReport.csv = summary<br> UnambNegTable.csv = counts of unique cuts on the reverse strand<br> UnambPosTable.csv = counts of unique cuts on the forward strand<br> AmbPosTable.csv = counts of all cuts on the forward strand<br> AmbNegTable.csv = counts of all cuts on the reverse strand</p> <p> </p>
Role of Alkylhydroperoxidase Rv2159c in the Oxidative Stress Response and Virulence of Mycobacterium tuberculosis
<p><em>Mycobacterium tuberculosis</em>, which causes tuberculosis, is one of the leading infectious agents worldwide with a high rate of mortality. Following aerosol inhalation, <em>M. tuberculosis</em> primarily infects the alveolar macrophages, which results in a host immune response that gradually activates various antimicrobial mechanisms, including the production of reactive oxygen species (ROS), within the phagocytes to neutralize the bacteria. <em>OxyR</em> is the master regulator of oxidative stress response in several bacterial species. However, due to the absence of a functional <em>oxyR </em>locus in <em>M. tuberculosis,</em> the peroxidase stress is controlled by alkylhydroperoxidases. <em>M. tuberculosis </em>expresses alkylhydroperoxide reductase to counteract the toxic effects of ROS. In the current study, we report the functional characterization of an ortholgue of alkylhydroperoxidase family member, Rv2159c, a conserved protein with putative peroxidase activity, during stress response and virulence of <em>M. tuberculosis</em><em>. </em>We generated a gene knockout mutant of <em>M. tuberculosis </em>Rv2159c (MtbΔ2159) by specialized transduction. The MtbΔ2159 was sensitive to oxidative stress and exposure to toxic transition metals. In a human monocyte (THP-1) cell infection model, MtbΔ2159 showed reduced intracellular survival and increased expression of pro-inflammatory molecules, includingIL-1β, IP-10 and MIP-1α, compared to the wild type <em>M. tuberculosis</em> and Rv2159c-complemented MtbΔ2159 strains. Similarly, in a guinea pig model of pulmonary infection, MtbΔ2159 displayed growth attenuation in the lungs, compared to the wild type <em>M. tuberculosis</em> and Rv2159c-complemented MtbΔ2159 strains<em>. </em>Our study suggests that Rv2159c has a significant role in maintaining the cellular homeostasis during stress and virulence of <em>M. tuberculosis</em>. </p>
MR1-restricted T-cell clonotypes are associated with 'resistance' to Mycobacterium Tuberculosis infection - TRA/D immunoSEQ
<p><strong>Summary</strong></p> <ul> <li>Number of files: 39</li> <li>Data format: tsv</li> <li>Data type: TCRA/D immunoSEQ (Adaptive Biotechnologies)</li> <li>immunoSEQ version: v2</li> <li>Sample type: peripheral blood mononuclear cells (PBMCs)</li> <li>Genomic DNA extraction protocol: QIAGEN DNeasy Blood and Tissue kit</li> </ul> <p><strong>Sample description</strong></p> <p>Peripheral blood samples were collected from participants enrolled in a longitudinal cohort study based in Uganda. Donors were classified as either "resistors" (RSTRs, n = 19, defined as concordantly negative for tuberculin skin test and IFNg release assay despite high environmental exposure) or latently infected with M. Tuberculosis (LTBI, n = 20, concordantly as longitudinally positive for tuberculin skin test and IFNg release assay). Genomic DNA (gDNA) was extracted from cryopreserved PBMCs without stimulation or enrichment of T-cells using the Quiagen DNeasy Blood and Tissue kit. Protocol can be found at: https://www.qiagen.com/us/products/discovery-and-translational-research/dna-rna-purification/dna-purification/genomic-dna/dneasy-blood-and-tissue-kit </p>
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Allen Brain Atlas
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DANDI Archive for NWB datasets
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International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.