Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health threat affecting millions worldwide. Researchers can unravel intricate molecular networks through sophisticated bioinformatics and systems biology approaches, revealing key pathways and cellular processes involved in TB pathogenesis. This knowledge helps researchers understand how the bacteria evade the host's immune response, identify critical intervention points, and develop strategies to modulate the host's immune system to combat TB infection effectively.

The ‘Monthly Dataset Roundup’ series is back; this time, we are delving into TB research! As part of our mission to share high-quality datasets to facilitate the reuse of multi-omics data, we are excited to present interesting datasets that capture TB's comprehensive molecular landscape. These datasets, encompassing multi-omics information, gene expression profiles, drug resistance patterns, and host-pathogen interactions, are crucial to unlocking the secrets of TB's pathogenesis and facilitating targeted interventions. Find more curated datasets on TB that can be visualized and analyzed using our biomedical data platform, Polly.

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Dataset 1

Prevention of tuberculosis in macaques after intravenous BCG immunization

Dataset ID: SCP796_1
Year of Publication: 2020
Total Samples: 30
Experiment type: Single-cell RNA Sequencing
Organism: Macaca mulatta
Reference link: Publication, Raw data

Summary:

Mtb is the leading cause of death from infection worldwide. Intradermal (ID) vaccination with Bacille Calmette-Guérin (BCG) has variable efficacy against pulmonary TB, the primary reason for mortality and disease transmission. Here the authors show that the route and dose of BCG vaccination alters circulating and lung resident T cells and subsequent protection against Mtb challenge in nonhuman primates (NHP). NHP immunized with BCG by the intravenous (IV) route induced substantially higher antigen-specific CD4 (Th1 or Th17) and CD8 responses in blood, spleen, bronchoalveolar lavage, and lung lymph nodes compared to the same BCG dose administered by ID or aerosol routes. Moreover, IV immunization was the only route that induced a high frequency of antigen-specific tissue-resident T cells in lung parenchyma. Six months after BCG vaccination, NHP were challenged with virulent Mtb. Strikingly, 9 of 10 NHP that received BCG IV were highly protected, with 6 NHP showing no detectable infection as determined by Positron Emission Tomography-Computed Tomography imaging, mycobacterial growth, pathology, granuloma formation, or de novo immune responses to Mtb-specific antigens. The finding that BCG IV prevents or significantly limits Mtb infection in NHP has important implications for vaccine development. It provides a model for determining immune correlates and mechanisms of protection against TB.

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Dataset 2

SARS-CoV-2 Receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues

Dataset ID: SCP814_Human_Lung
Year of Publication: 2020
Total Samples: 21
Experiment type: Single-cell RNA Sequencing
Organism: Homo sapiens
Reference link: Publication, Raw data

Summary:

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) that causes COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) and, in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, the authors leverage human, NHP, and mouse scRNA-seq datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. Within this cohort of donors, 3 individuals were human immunodeficiency virus (HIV)⁺ and diagnosed with active TB, 3 donors had active TB and were HIV⁻, and 2 were negative for both pathogens. It was observed that all of the ACE2⁺ cells across all cell types were derived from HIV⁺ Mtb⁺ donors despite approximately equivalent recovery of epithelial cell types from all donors. The study identified ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, it was discovered that ACE2 is a human interferon-stimulated gene in vitro using airway epithelial cells and extending our findings to in vivo viral infections. The data suggest that SARS-CoV-2 could enhance condition by exploiting species-specific interferon (IFN) -driven upregulation of ACE2, a tissue-protective mediator during lung injury.

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Dataset 3

Immune dysfunction in intermediate hyperglycaemia and diabetes patients in tuberculosis

Dataset ID: GSE114192_GPL18573_raw
Year of Publication: 2020
Total Samples: 254
Experiment type: Bulk-RNA sequencing
Organism: Homo sapiens
Reference link: Publication, Raw data

Summary:

People living with diabetes have an increased risk of developing active TB. The effects of diabetes/ Hemoglobin A1c (HbA1c also known as Glycated Hemoglobin) (HbA1c ≥6.5%) and intermediate hyperglycemia (HbA1c 5.7-6.5%) on this transcriptomic signature were investigated by RNA-seq to enhance the understanding of immunological susceptibility in diabetes-TB comorbidity. Diabetes increased the magnitude of gene expression change in the host transcriptome in TB, characterized by an increase in innate and a decrease in adaptive immune responses. Strikingly, patients with intermediate hyperglycemia and TB exhibited blood transcriptomes much more similar to diabetes-tuberculosis patients than uncomplicated tuberculosis patients. Aberrant transcriptomes unveiled a susceptibility mechanism of diabetes patients to TB of enhanced inflammation and reduced interferon responses.

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Dataset 4

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment

Dataset ID: GSE193979_GPL18573_raw
Year of Publication: 2022
Total Samples: 212
Experiment type: Bulk-RNA sequencing
Organism: Homo sapiens
Reference link: Publication, Raw data

Summary:

Globally, the anti-TB treatment success rate is approximately 85%, with treatment failure, relapse, and death occurring in a significant proportion of pulmonary TB patients. Treatment success rates are lower among people with diabetes. Predicting treatment failure early after diagnosis would allow early treatment adaptation and may improve global TB control. Samples were collected in a longitudinal cohort study of adult TB patients with or without concomitant DM from South Africa and Indonesia to characterize whole blood transcriptional profiles before and during anti-TB treatment, using unbiased RNA-Seq and targeted gene Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dcRT-MLPA). The authors reported differences in entire blood transcriptome profiles between patients with a good versus poor anti-TB treatment outcome, observed before and throughout treatment initiation. An eight-gene and 22-gene blood transcriptional signatures distinguished patients with a good treatment outcome from patients with a poor treatment outcome at diagnosis (AUC=0·815) or two weeks (AUC=0·834) after initiating anti-TB treatment, respectively. Importantly, high accuracy was obtained by cross-validating this signature in an external cohort (AUC=0·749). These findings suggest that transcriptional profiles can be used as a prognostic biomarker for treatment failure and success, even in patients with concomitant DM.

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Dataset 5

Leukocyte - endothelial cell interaction in infections: The role of IL1, TNF, and IFN pathways

Dataset ID: GSE131590_GPL18573_raw
Year of Publication: 2021
Total Samples: 138
Experiment type: Bulk-RNA sequencing
Organism: Homo sapiens
Reference link: Publication, Raw data

Summary:

In this study the authors comprehensively characterized the transcriptomic responses of human leukocytes (PBMC stimulation) and endothelial cell (EC) to Gram negative-bacteria, Gram positive-bacteria, and fungi by RNAseq. They showed that the typical response of leukocytes to various pathogens converges on EC activation. By exposing EC to leukocyte-released mediators, with or without the presence of Interleukin-1 receptor antagonist (IL1RA) and Tumor necrosis factor alpha (TNFα) antibodies, specific roles for IL1 and TNFα were identified in driving the majority of, but not exclusively, endothelial activation. Furthermore, leukocyte-released mediators strongly induce interferon pathways in EC but independently from IL1 and TNFα. The study, therefore, reveals a role for IFN, together with IL1 and TNFα signaling, in mediating leukocyte-endothelial interaction in infections.

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