Unknown,Transcriptomics,Genomics,Proteomics

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Blood Transcriptional Profiling of a prospective HIV-negative UK Cohort of Tuberculosis Contacts


ABSTRACT: Blood transcriptional signatures may predate clinical diagnosis and detect subclinical incipient tuberculosis (TB) disease. To validate such blood signatures, close contacts of TB patients were recruited from multiple TB clinics in London. Close contacts of active TB were defined as individuals with a cumulative duration of exposure of greater than eight hours in a confined space to the index case prior to initiation of treatment. Known human immunodeficiency virus (HIV)-positive patients were excluded. At enrolment, interferon gamma release assays (IGRAs) were done using the QuantiFERON-TB Plus assay (Qiagen, Germany), and peripheral blood was collected into Tempus tubes for whole genome transcriptional profiling by RNA sequencing. Participants who progressed to active TB were identified by linkage with the national electronic TB register. Local case notes were reviewed to identify individuals who had received preventative treatment. This submission contains data from n=360 adult participants, of which n=9 progressed to TB during a median follow-up time of 1.9 years. The data were used for two publications: The first publication (Roe et al 2019) makes use of an initial subset of n=333 participants, of which n=6 progressed to TB during the median follow-up time of 346 days. In the second publication (Gupta et al 2019), we extended the dataset to n=360 participants and the median follow-up time to 1.9 years; n=3 initial non-progressors progressed to TB during this extended follow-up.

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Cristina Venturini 

PROVIDER: E-MTAB-6845 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Blood Transcriptomic Stratification of Short-term Risk in Contacts of Tuberculosis.

Roe Jennifer J   Venturini Cristina C   Gupta Rishi K RK   Gurry Celine C   Chain Benjamin M BM   Sun Yuxin Y   Southern Jo J   Jackson Charlotte C   Lipman Marc C MC   Miller Robert F RF   Martineau Adrian R AR   Abubakar Ibrahim I   Noursadeghi Mahdad M  

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200201 5


<h4>Background</h4>The highest risk of tuberculosis arises in the first few months after exposure. We reasoned that this risk reflects incipient disease among tuberculosis contacts. Blood transcriptional biomarkers of tuberculosis may predate clinical diagnosis, suggesting they offer improved sensitivity to detect subclinical incipient disease. Therefore, we sought to test the hypothesis that refined blood transcriptional biomarkers of active tuberculosis will improve stratification of short-ter  ...[more]

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