Developing gene signature against Mycobacterium bovis infection in Cattle
Ontology highlight
ABSTRACT:
ORGANISM(S): Bos indicus Bos taurus Bubalus bubalis Bos primigenius
PROVIDER: GSE74050 | GEO | 2016/10/25
SECONDARY ACCESSION(S): PRJNA298874
REPOSITORIES: GEO
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Project description:The bTB research programme is centred on identifying the genetic basis for resistance against bovine tuberculosis and towards diagnostics Agilent Whole Genome Bovine 8x60k Gene Expression (AMADID: 29411) , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)
2016-10-25 | E-GEOD-74050 | biostudies-arrayexpress
Project description:Background: Bovine tuberculosis is an enduring disease of cattle that has significant repercussions for human health. The advent of high-throughput functional genomics technologies has facilitated large-scale analyses of the immune response to this disease that will ultimately lead to novel diagnostics and therapeutic targets. Analysis of mRNA abundance in peripheral blood mononuclear cells (PBMC) from six Mycobacterium bovis infected cattle and six non-infected controls was performed. A targeted immunospecific bovine cDNA microarray with duplicated spot features representing 1,391 genes was used to test the hypothesis that a novel gene expression profile may exist in M. bovis infected animals in vivo. Results: In total, 378 gene features were differentially expressed at the P ≤ 0.05 level in bovine tuberculosis (BTB)-infected and control animals, of which 244 were expressed at lower levels (65%) in the infected group. Lower relative expression of key innate immune genes such as the Toll-like receptor 2 (TLR2) and TLR4 genes, lack of differential expression of indicator adaptive immune gene transcripts (IFNG, IL2, IL4), and lower BOLA major histocompatability complex – class I (BOLA) and class II (BOLA-DRA) gene expression was consistent with innate immune gene repression in the BTB-infected animals. Supervised hierarchical cluster analysis and class prediction validation identified a panel of 15 genes predictive of disease status and selected gene transcripts were validated (n = 8 per group) by real time quantitative reverse transcription PCR. Conclusion: These results suggest that large-scale expression profiling can identify gene signatures of disease in peripheral blood that can be used to classify animals on the basis of in vivo infection, in the absence of exogenous antigenic stimulation. Keywords: Disease state analysis
2007-10-16 | GSE8857 | GEO
Project description:Bovine tuberculosis (BTB) caused by Mycobacterium bovis continues to cause substantial losses to global agriculture and has significant repercussions for human health. The advent of high throughput genomics has facilitated large scale gene expression analyses that present a novel opportunity for revealing the molecular mechanisms underlying chronic mycobacterial infection. Using this approach, we have previously shown that innate immune genes in peripheral blood mononuclear cells (PBMC) from BTB-infected animals are repressed in vivo in the absence of exogenous stimulation. In the present study, functional genomics methods were used to examine the immune response of PBMC from BTB-infected (n = 6) and healthy control (n = 6) cattle to stimulation with bovine purified protein derivative (PPDb) in vitro. PBMC were harvested before, and at 3h and 12h post in vitro stimulation with PPDb. Gene expression changes were catalogued within each group using a reference hybridization design and a targeted immunospecific cDNA microarray platform (BOTL-5) with 4,800 spot features representing 1,391 genes
2008-09-20 | GSE12835 | GEO
Project description:Background: Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix® GeneChip® Bovine Genome Array with features representing more than 23,000 gene transcripts and over 19,000 gene probe sets. Results: Control and infected animals had similar mean white blood cell counts. However, the mean number of lymphocytes was significantly increased in the infected group relative to the control group (P = 0.001), while the mean number of monocytes was significantly decreased in the BTB group (P = 0.002). Hierarchical clustering analysis using gene expression data from all 5,388 detectable mRNA transcripts unambiguously partitioned the animals according to their disease status. In total, 2,960 gene transcripts were differentially expressed (DE) between the infected and control animal groups (adjusted P-value threshold ≤ 0.05); with the number of genes showing decreased relative expression (1,563) exceeding those displaying increased relative expression (1,397). Systems analysis using the Ingenuity Systems Pathway Analysis (IPA) Knowledge Base revealed an over-representation of DE genes involved in the immune response functional category. More specifically, 64.5% of genes in the affects immune response subcategory displayed decreased relative expression levels in the infected animals compared to the control group. Conclusions: This study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection Affymetrix GeneChip® Bovine Genome Arrays were used to examine gene expression of peripheral blood leukocytes from cattle infected with Mycobacterium bovis
2011-12-01 | E-GEOD-33359 | biostudies-arrayexpress
Project description:Background: Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix® GeneChip® Bovine Genome Array with features representing more than 23,000 gene transcripts and over 19,000 gene probe sets. Results: Control and infected animals had similar mean white blood cell counts. However, the mean number of lymphocytes was significantly increased in the infected group relative to the control group (P = 0.001), while the mean number of monocytes was significantly decreased in the BTB group (P = 0.002). Hierarchical clustering analysis using gene expression data from all 5,388 detectable mRNA transcripts unambiguously partitioned the animals according to their disease status. In total, 2,960 gene transcripts were differentially expressed (DE) between the infected and control animal groups (adjusted P-value threshold ≤ 0.05); with the number of genes showing decreased relative expression (1,563) exceeding those displaying increased relative expression (1,397). Systems analysis using the Ingenuity Systems Pathway Analysis (IPA) Knowledge Base revealed an over-representation of DE genes involved in the immune response functional category. More specifically, 64.5% of genes in the affects immune response subcategory displayed decreased relative expression levels in the infected animals compared to the control group. Conclusions: This study demonstrates that genome-wide transcriptional profiling of PBL can distinguish active M. bovis-infected animals from control non-infected animals. Furthermore, the results obtained support previous investigations demonstrating that mycobacterial infection is associated with host transcriptional suppression. These data support the use of transcriptomic technologies to enable the identification of robust, reliable transcriptional markers of active M. bovis infection
2011-12-01 | GSE33359 | GEO
Project description:Bovine tuberculosis (bTB), primarily caused by Mycobacterium bovis (M. bovis), is a globally zoonotic disease with significant economic impacts. Plasma exosomes have been extensively used for investigating disease processes and exploring biomarkers. While mass spectrometry (MS)-based proteomic analysis of plasma exosomes has been employed for human tuberculosis (TB) studies, it has not yet been applied to bTB. Therefore, a comprehensive proteomic overview of plasma exosomes from M. bovis-infected cows is essential. In this study, we present an extensive proteomic analysis of plasma exosomes from 89 M. bovis-infected cows across three farms, using data-dependent acquisition (DDA) mode. Our analysis encompasses 239,894 spectra, 6,011 peptides and 835 protein groups. The proteomic overview reveals both consistencies and differences among individual cows, supplements 595 proteins to the bovine exosome library, and enriches tuberculosis and related pathways. Additionally, six pathways were validated as immune response pathways, and three proteins (CATHL1, H1-1, and LCN2) were identified as potential indicators of bTB. This study is the first to investigate the exosome proteome of plasma from cows infected with M. bovis, providing a valuable dataset for exploring candidate bTB markers and understanding the mechanisms of host defense against M. bovis.
2024-06-17 | PXD048167 |
Project description:Abstract: Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to cause significant issues for the global agriculture industry as well as for human health. An incomplete understanding of the host immune response contributes to the challenges of control and eradication of this zoonotic disease. In this study, high-throughput bulk RNA sequencing (RNA-seq) was used to characterize differential gene expression in γδ T cells – a subgroup of T cells which bridge innate and adaptive immunity and have specific anti-mycobacterial response mechanisms. γδ T cell subsets are classified on the basis of expression of a pathogen-recognition receptor known as Workshop Cluster 1 (WC1) and we hypothesised that bTB infection may alter the phenotype and function of specific γδ T cell subsets. Peripheral blood was collected from naturally M. bovis-infected (positive for single intradermal comparative tuberculin test (SICTT) and IFN-γ ELISA) and age- and sex-matched, non-infected control Holstein-Friesian cattle. γδ T subsets were isolated using fluorescence activated cell sorting (n = 10-12 per group) and high-quality RNA extracted from each purified lymphocyte subset (WC1.1+, WC1.2+, WC1- and γδ-) was used to generate transcriptomes using bulk RNA-seq (n = 6 per group, representing a total of 48 RNA-seq libraries). Relatively low numbers of differentially expressed genes (DEGs) were observed between most cell subsets; however, 163 genes were significantly differentially expressed in the M. bovis-infected compared to control groups for the WC1.1+ γδ T cell compartment (Log 2 FC ≥ 1.5 and FDR P adj ≤ 0.1). The majority of these DEGs (146) were significantly increased in expression in cells from the bTB+ cattle and included genes encoding transcription factor (TBX21 and EOMES), chemokine receptors (CCR5 and CCR7), granzymes (GZMA, GZMM and GZMH) and multiple killer cell immunoglobulin-like receptors (KIR) indicating cytotoxic functions. Biological pathway overrepresentation analysis revealed enrichment of genes with multiple immune functions including cell activation, proliferation, chemotaxis and cytotoxicity of lymphocytes. In conclusion, WC1.1+ γδ T cells have been proposed as major regulatory cell subset in cattle, and we provide evidence for preferential differential activation of this specific subset in cattle naturally infected with M. bovis. Understanding the role of these critical immune cells during mycobacterial infection contributes to our understanding of host immunity to bTB and identifies multiple novel cytotoxic functions of WC1.1+ γδ T cells.
2023-07-01 | E-MTAB-13111 | biostudies-arrayexpress
Project description:Tuberculin Skin Test (TST) based on in vivo intradermal inoculation of purified protein derivative from M. bovis (bPPD) is the diagnostic test for the control and surveillance of bovine tuberculosis (bTB). Proteomic analyses were performed on four bPPD samples from Mycobacterium bovis, strain AN5. Proteins were precipitated from bPPD solutions by TCA precipitation. The proteome of four bPPD preparations was investigated by bottom-up proteomics, which consisted in protein digestion and nano-LC-MS/MS analysis. Mass spectrometry analysis was performed on a Q-Exactive Hybrid Quadrupole-Orbitrap Mass Spectrometer coupled online to an Easy nano-LC1000 system. This study represents the highest proteome coverage of bPPD preparations to date. Since proteins perform cellular functions essential to health and/or disease, obtaining knowledge of their presence and variance is of great importance in understanding disease states and for advancing translational studies. Therefore, to better understand Mycobacterium tuberculosis complex biology during infection, survival, and persistence, the reproducible evaluation of the proteins that catalyze and control these processes is critically important. More active and more specific tuberculins would be desirable. The cross-reactivity to non-tuberculous mycobacterium species (false-positive results) is crucial to develop better and more defined antigens.
2017-04-05 | PXD005920 | Pride
Project description:Bovine tuberculosis (bTB), caused by Mycobacterium bovis (Mycobacterium tuberculosis complex), is a zoonotic disease that affects cattle and wildlife worldwide. In some regions of Spain, Iberian red deer (Cervus elaphus hispanicus) can serve as reservoir of infection, thus increasing the risk of human and cattle exposure and infection. Mesenteric lymph nodes are naturally infected with M. bovis in Iberian red deer, in which the digestive route of infection is particularly important in Mediterranean Spain. In this study we characterized the differential expression of inflammatory and immune response genes in mesenteric lymph nodes of Iberian red deer naturally infected with M. bovis using a Ruminant Immuno-inflammatory Gene Universal Array (RIGUA) and real-time RT-PCR. Of the 600 genes that were analyzed in the microarray, 157 showed ≥ 1.2 fold changes in expression in infected or uninfected deer and 17 genes displayed an expression fold change greater than 1.7 with a P-value ≤ 0.05 and were selected for further analysis. These genes included tight junction proteins (Z02 and occluding), IL-11R, bactenecin, CD62L, CD74, desmoglein, IgA and IgM that constitute new findings and suggest new mechanisms by which M. bovis may modulate host inflammatory and immune responses. Identification of genes differentially expressed in animals and tissues naturally infected with M. bovis contributes to our basic understanding of the mechanisms of pathogenesis and protective immunity to mycobacterial infections and may have important implications for future functional genomic and vaccine studies to aid in the control of bTB in deer and other wildlife reservoir species. Keywords: disease state analysis
2007-10-17 | GSE6083 | GEO
Project description:Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis infected animals and detect 2,592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis¬-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 132 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.
2024-02-26 | GSE255724 | GEO