RNA-seq of Human Tuberculosis (TB) in active TB patients, contacts with latent infection and uninfected contacts
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ABSTRACT: 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: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: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.
Project description:Monocytes and granulocytes were isolated from blood of TB patients and household contacts. RNA was isolated and microRNA expression was measured using microarrays. House-hold contacts were matched to TB patients by gender and age. From each subject, two profiles (monocytes and granulocytes) were collected.
Project description:Monocytes and granulocytes were isolated from blood of TB patients and household contacts. RNA was isolated and gene expression was measured using microarrays. House-hold contacts were matched to TB patients by gender and age. From each subject, two profiles (monocytes and granulocytes) were collected.
Project description:This study consists of 10 whole genome RNA-seq profiles which have been generated from blood samples collected from ten different volunteers in the Personal Genome Project UK
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:In the present study, we used a high-throughput small RNA deep sequencing followed by a systematic computational analysis to identify genome wide mutant p53R273H regulated miRNAs in both DNA damage dependent and independent context. Several miRNA-mRNA regulatory networks have been predicted that might contribute to mutant p53 GOF properties. Differentially regulated miRNA signature profile has been validated in the lung cancer patients harboring wildtype and mutant p53. We identified specific miRNA signatures for lymph node metastasis associated with p53 mutation in lung adenocarcinoma and also predicted the possible contribution of two mutant p53 regulated miRNAs in EMT process. Furthermore, this study identified a hitherto unknown miRNA in human which might act as one of the crucial downstream targets of GOF mutant p53 to confer oncogenic properties. Determination of mutant p53R273H regulated microRNAs H1299 cells.
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.
Project description:Chromosomal instability (CIN) refers to the rate at which cells are unable to properly segregate whole chromosomes, leading to aneuploidy. Using young to old-aged human dermal fibroblasts, we observed a dysfunction of the mitotic machinery arising with age that mildly perturbs chromosome segregation fidelity and contributes to the generation of fully senescent cells. Here, we found that elderly cells have an increased number of stable kinetochore-microtubule (k-MT) attachments and decreased efficiency in the correction of improper k-MT interactions. Importantly, chromosome mis-segregation rates in old-aged cells decreased upon both genetic and small molecule enhancement of MT-depolymerizing kinesin-13 activity. Notably, restored chromosome segregation accuracy inhibited the phenotypes of cellular senescence.
Project description:Monocytes and granulocytes were isolated from blood of TB patients and household contacts. RNA was isolated and gene expression was measured using microarrays.