Gene expression analysis of anti-tuberculous drug responses in a whole blood transcriptome model
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PROVIDER: PRJNA598207 | ENA |
REPOSITORIES: ENA
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Project description:There is a need for better tools to evaluate new or repurposed TB drugs. The whole blood bactericidal activity (WBA) assay has been advocated for this purpose. We investigated whether transcriptional responses in the WBA assay resemble TB responses in vivo, and whether the approach might additionally reveal mechanisms of response. Microarray analysis was performed on Mycobacterium tuberculosis (Mtb) RNA extracted from whole blood cultures, sputum from TB patients on combination treatment, and drug-free broth cultures
2020-03-23 | GSE142756 | GEO
Project description:BackgroundThere is a need for better tools to evaluate new or repurposed TB drugs. The whole blood bactericidal activity (WBA) assay has been advocated for this purpose. We investigated whether transcriptional responses in the WBA assay resemble TB responses in vivo, and whether the approach might additionally reveal mechanisms of action.Results1422 of 1798 (79%) of differentially expressed genes in WBA incubated with the standard combination of rifampicin, isoniazid, pyrazinamide and ethambutol were also expressed in sputum (P < 0.0001) obtained from patients taking the same combination of drugs; these comprised well-established treatment-response genes. Gene expression profiles in WBA incubated with the standard drugs individually, or with moxifloxacin or faropenem (with amoxicillin and clavulanic acid) clustered by individual drug exposure. Distinct pathways were detected for individual drugs, although only with isoniazid did these relate to known mechanisms of drug action.ConclusionsSubstantial agreement between whole blood cultures and sputum and the ability to differentiate individual drugs suggest that transcriptomics may add value to the whole blood assay for evaluating new TB drugs.
| S-EPMC7140558 | biostudies-literature
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups. Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.!Series_type = Expression profiling by array
2011-06-30 | E-GEOD-23074 | biostudies-arrayexpress
Project description:Purpose: To determine whether and how pleural macrophages change in phenotype, transcription and function in patients with tuberculous pleuritis following anti-TB antibiotic treatment.
2017-07-01 | GSE85037 | GEO
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.
2011-07-01 | GSE23074 | GEO
Project description:Transcriptomics-based anti-tuberculous mechanism of traditional Chinese polyherbal preparation NiuBeiXiaoHe intermediates
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Project description:Whole blood transcriptional profiles in children with or without tuberculous meningitis (TBM) were compared using RNA-Seq and a biomarker signature driven by inflammasome activation and signaling was identified
2019-08-06 | GSE111459 | GEO
Project description:Cerebrospinal fluid transcriptional profiles in children with tuberculous meningitis (TBM) or other infections were compared using RNA-Seq and a biomarker signature driven by NMDA-receptor activation was identified
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Project description:Genome wide DNA methylation profiling of normal and colon cancer and assosiation study between anti-cancer drug respond group and non-respond group. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in 118 paired anti-cancer drug response tested colon cancer and adjacent normal tissues Bisulphite converted DNA from the 248 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
2011-12-31 | E-GEOD-27130 | biostudies-arrayexpress
Project description:Tuberculosis co-infected with HIV may increase the risk of causing meningitis. Tuberculous meningitis co-infected with HIV associated with high mortality and severe neurological abnormalities in affected individuals. We have carried out TBM co-infected with HIV gene expression study using whole human genome microarrays. We identified 796 differentially expressed genes with fold change cut off of 2 or more than 2. Out of 796 differentially expressed genes, 398 were upregulated and 396 were downregulated. We have validated two molecules from microarray data using immunohistochemistry. The proposed study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis coinfected with HIV and four head injury cases were used as controls. We have used 4X44K arrays from agilent platform. To validate our microarray results, we have done immunohistochemistry on 10 TBM+HIV cases and 10 control groups.
2012-12-31 | E-GEOD-29507 | biostudies-arrayexpress