Description: Description from BioProject: "The lifecycle of M. tuberculosis within the human host is marked by critical transition points between the major phases of infection: Initial infection, latent disease, active tuberculosis, and resolution with antibiotic therapy. Through observation of patients in each of these stages, we have some knowledge about host determinants that maintain each of these stages, such as the need for sufficient CD4 T cells, interferon gamma and tumor necrosis factor alpha in the control of latency. However, the vast majority of HIV negative TB patients do not have defined deficiencies in these immune factors and therefore the host determinants of the heterogeneous ability of TB patients to control M. tuberculosis infection, either in the context of initial infection after exposure, reactivation of latent infection, or relapse-free elimination of M. tuberculosis after antimicrobial therapy, are unknown. To address these knowledge gaps, we have assembled a set of patient cohorts to examine three interrelated host factors that we hypothesize may contribute to the heterogeneity in host control of M. tuberculosis during the transition from uninfected> LTBl and infected>cured. These factors are Mucosal Associated Invariant T (MAIT) cells, whole blood transcriptomic signatures, and stool microbiomic composition. We will initially examine these factors in two cohorts of TB patients: 1) Patients either resistant to initial infection or recently infected from a household contact, a comparison which will yield correlates of innate resistance to infection and 2) Patients undergoing therapy for active pulmonary tuberculosis, either with short course monotherapy or standard multidrug therapy, to determine correlates of clearance of replicating and persister M. tuberculosis. We anticipate that these studies will provide a set of quantitative molecular assays that will both expand our knowledge ofthe heterogeneity of host control of M. tuberculosis infection, and potentially supply biomarkers that will allow identification of patients resistant to infection, destined to reactivate from latency, or to relapse after antimicrobial therapy."https://datacatalog.mskcc.org/add/SubjectDomain?modal=true

Subject of Study

Homo sapiens

Mycobacterium tuberculosis

Subject(s)

Gastrointestinal Microbiome

Mucosal-Associated Invariant T Cells

Tuberculosis

Access via BioProject
Links whole genome, amplicon and RNA sequencing results from 411 experiments
Accession #: PRJNA445968
Access Restrictions: Free to All
Access Instructions: The NCBI BioProject and SRA databases provide open access to these files.
Associated Publications: Wipperman M, Bhattarai S, Vorkas C, et al. Gastrointestinal microbiota composition predicts peripheral inflammatory state during treatment of human tuberculosis. Nature Communications. 2021; 12:1141.

Vorkas C, Wipperman M, Li K, et al. Mucosal-associated invariant and γδ T cell subsets respond to initial Mycobacterium tuberculosis infection. JCI Insight. 2018; 3(19):e121899.
Data Type: Genomic
Equipment Used: Illumina HiSeq 2000
High throughput gene sequencing system

Illumina HiSeq 4000
High throughput gene sequencing system

Illumina MiSeq (Mus musculus)
Software Used: SRA Toolkit
The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.
Dataset Format(s): FASTQ
Data Tool(s): RNA Seq

WGS

Amplicon Sequencing
Dataset Size: 955 GB

Data Catalog Record Updated: 2021-07-22

Innate, Transcriptomic, and Microbiomic Correlates of Tuberculosis Infection and Disease