Project description:RNA-sequencing was performed on baseline blood samples from HIV-infected and HIV-uninfected asymptomatic adults with recent household exposure to an index case of infectious pulmonary tuberculosis (TB) and with detectable Mtb DNA in PBMC. Additional sequencing was also performed on follow-up blood samples from HIV-infected participants following completion of isoniazid preventative therapy.
Project description:Whole-blood RNA from active TB patients and their contacts (uninfected and with latent infection) was sequenced to study the different gene expression profile on each group. Differentially expressed genes could be used as potential diagnostic tools and provide information of the spectrum of TB disease.
Project description: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.
Project description:Diagnosis of TB, especially in the presence of an HIV co-infection, can be challenging when using conventional diagnostic methods. In this study, we analyzed global gene expression data from PBMC of patients that were either mono-infected with HIV or co-infected with HIV and TB in order to identify a TB-specific gene signature.
Project description:Diagnosis of TB, especially in the presence of an HIV co-infection, can be challenging when using conventional diagnostic methods. In this study, we analyzed global gene expression data from PBMC of patients that were either mono-infected with HIV or co-infected with HIV and TB in order to identify a TB-specific gene signature. Total RNA obtained from PBMC from a South African cohort. Microarry analysis was performed to compare gene expression in patients either infected with HIV or co-infected with HIV/TB.
Project description:Genome wide DNA methylation profiling of PBMC from South African patients either infected with HIV only or coinfected with HIV and tuberculosis (TB). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles from PBMC samples. Samples included 19 HIV patients and 20 HIV/TB co-infected patients.
Project description:Genome wide DNA methylation profiling of PBMC from South African patients either infected with HIV only or coinfected with HIV and tuberculosis (TB). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles from PBMC samples. Samples included 19 HIV patients and 20 HIV/TB co-infected patients. Bisulphite converted DNA were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
Project description:Monocytes and granulocytes were isolated from blood of TB patients and household contacts. DNA was isolated and methylation profile was measured using Illumina HumanMethylation450. House-hold contacts were matched to TB patients by gender and age. From each subject, two profiles (monocytes and granulocytes) were collected.