Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA288792 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Even though recent reports estimate a reduction in the spread and contraction of Tuberculosis (TB), 30 % of the world population are currently being latently infected by Mycobacterium tuberculosis (Mtb). This latent infection can at any time develop into active disease. Biomarkers to monitor this process as well as biomarkers for disease susceptibility and TB diagnosis is urgently needed in order to facilitate a more drastic decrease in the spread of Mtb and better care for TB patients. Our understanding of biology combined with evolving technical advances in high-throughput techniques, led us to investigate the possibility of additional role players (epigenetics and proteomics) in the quest to (a) understand the biology of TB host response and (b) search for biomarkers in TB diagnostics and –susceptibility. We engaged in a pilot study, using a relatively small sample set to interrogate the DNA methylome, transcriptome and proteome in monocytes and granulocytes of TB patients and healthy latently infected participants. The observations in this study provide a first glimpse at the level- and sources of diversity in the epigenome and proteome amongst TB patients and latently infected controls despite limitations due to small sample size. Functionally the differences between the disease phenotypes observed in the different platforms were congruent and suggest regulation of function not only at the transcriptional level, but also by DNA methylation and microRNA. We conclude that the current data support the notion to develop a large scale study of especially the DNA methylome while care should be taken in the study design to account for variation based on gender, age and cell type.
2015-08-26 | PXD001960 | Pride
Project description:UnlabelledAn estimated one-third of the world's population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based on transcriptomics. Our understanding of biology combined with evolving technical advances in high-throughput techniques led us to investigate the possibility of additional platforms (epigenetics and proteomics) in the quest to (i) understand the biology of the TB host response and (ii) search for multiplatform biosignatures in TB. We engaged in a pilot study to interrogate the DNA methylome, transcriptome, and proteome in selected monocytes and granulocytes from TB patients and healthy LTBI participants. Our study provides first insights into the levels and sources of diversity in the epigenome and proteome among TB patients and LTBI controls, despite limitations due to small sample size. Functionally the differences between the infection phenotypes (LTBI versus active TB) observed in the different platforms were congruent, thereby suggesting regulation of function not only at the transcriptional level but also by DNA methylation and microRNA. Thus, our data argue for the development of a large-scale study of the DNA methylome, with particular attention to study design in accounting for variation based on gender, age, and cell type.ImportanceDNA methylation modifies the transcriptional program of cells. We have focused on two major populations of leukocytes involved in immune response to infectious diseases, granulocytes and monocytes, both of which are professional phagocytes that engulf and kill bacteria. We have interrogated how DNA methylation, gene expression, and protein translation differ in these two cell populations between healthy individuals and patients suffering from TB. To better understand the underlying biologic mechanisms, we harnessed a statistical enrichment analysis, taking advantage of predefined and well-characterized gene sets. Not only were there clear differences on various levels between the two populations, but there were also differences between TB patients and healthy controls in the transcriptome, proteome, and, for the first time, DNA methylome in these cells. Our pilot study emphasizes the value of a large-scale study of the DNA methylome taking into account our findings.
| S-EPMC4600108 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-08-22 | E-GEOD-70478 | biostudies-arrayexpress
Project description:Transcriptomics biomarkers in prostate cancer
| PRJNA827124 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2015-08-22 | GSE70478 | GEO
Project description:Regional transcriptomics and proteomics of DMPK genes in human intestine
| PRJNA889700 | ENA
Project description:Transcriptomics and proteomics analyses were carried out on rectal mucosal biopsies from 22 healthy adults with either optimal (n=11, mean plasma Se =1.43μmol/l, s.e.m ±0.06) or sub-optimal (n=11, mean plasma Se = 0.86umol/l, s.e.m ± 0.01) plasma Se status. Plasma Se status was associated with altered expression of 254 genes implicated in cancer, immune function and inflammatory response, cell growth and proliferation, cellular movement and cell death; 69 out of 254 genes had their expression significantly correlated with Se status, including two selenoprotein genes (SEPW1 and SELK). Proteomics identified 26 proteins differentially expressed between the two Se groups, including cytoskeletal proteins and factors involved in immune and inflammatory response and cancer pathways. Results from proteomics and transcriptomics support each other and integration of the two datasets was consistent with a reduced inflammatory and immune responses and a cytoskeleton remodelling in the rectal mucosa of individuals with sub-optimal Se status.
2015-12-31 | GSE70550 | GEO
Project description:Dissecting molecular pathways of neuropathology of PHTS by transcriptomics and proteomics
| PRJNA788867 | ENA
Project description:Quercetin has been shown to act as an anti-carcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterise transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 weeks. Transcriptome data analysed with Gene Set Enrichment Analysis showed that quercetin significantly downregulated the potentially oncogenic mitogen-activated protein kinase (Mapk) pathway. In addition, quercetin enhanced expression of tumor suppressor genes, including Pten, Tp53 and Msh2, and of cell cycle inhibitors, including Mutyh. Furthermore, dietary quercetin enhanced genes involved in phase I and II metabolism, including Fmo5, Ephx1, Ephx2 and Gpx2. Quercetin increased PPARα target genes, and concomitantly enhanced expression genes in volved in of mitochondrial fatty acid degradation. Proteomics performed in the same samples revealed 33 affected proteins, of which 4 glycolysis enzymes and 3 heatshock proteins were decreased. A proteome-transcriptome comparison showed a low correlation, but both pointed out towards altered energy metabolism. In conclusion, transcriptomics combined with proteomics showed that dietary quercetin evoked changes contrary to those found in colorectal carcinogenesis. These tumor-protective mechanisms were associated with a shift in energy production pathways, pointing at decreased glycolysis in the cytoplasm towards increased fatty acid degradation in the mitochondria. Keywords: Transscriptomics, proteomics, quercetin-exposed and control rats
2008-01-01 | GSE7479 | GEO