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Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches I

ABSTRACT: Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches I

PROVIDER: PRJNA804880 | ENA |

REPOSITORIES: ENA

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Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches

Project description:Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches

| PRJNA804874 | ENA

Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches II

Project description:Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches II

| PRJNA804879 | ENA

Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches II

Project description:Current therapeutic strategies against bacterial infections focus on reduction of pathogen load using antibiotics; however, stimulation of host tolerance to infection in the presence of pathogens might offer an alternative approach. We used computational transcriptomics and Xenopus laevis embryos to discover infection response pathways, identify potential tolerance inducer drugs, and validate their ability to induce broad tolerance. Xenopus exhibits natural tolerance to Acinetobacter baumanii, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae bacteria, whereas Aeromonas hydrophila and Pseudomonas aeruginosa produce lethal infections. Transcriptional profiling led to definition of a 20-gene signature that discriminates between tolerant and susceptible states, as well as identification of a more active tolerance response to gram negative compared to gram positive bacteria. Gene pathways associated with active tolerance in Xenopus, including some involved in metal ion binding and hypoxia, were found to be conserved across species, including mammals, and administration of a metal chelator (deferoxamine) or a HIF-1 agonist (1,4-DPCA) in embryos infected with lethal A. hydrophila increased survival despite high pathogen load. These data demonstrate the value of combining the Xenopus embryo infection model with computational multi-omics analyses for mechanistic discovery and drug repurposing to induce host tolerance to bacterial infections.

2022-06-16 | GSE196424 | GEO

Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches I

2022-06-16 | GSE196422 | GEO

Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-16 | GSE196425 | GEO

Enhancers of Host Immune Tolerance to Bacterial Infection Discovered Using Linked Computational and Experimental Approaches.

Project description:Current therapeutic strategies against bacterial infections focus on reduction of pathogen load using antibiotics; however, stimulation of host tolerance to infection in the presence of pathogens might offer an alternative approach. Computational transcriptomics and Xenopus laevis embryos are used to discover infection response pathways, identify potential tolerance inducer drugs, and validate their ability to induce broad tolerance. Xenopus exhibits natural tolerance to Acinetobacter baumanii, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae bacteria, whereas Aeromonas hydrophila and Pseudomonas aeruginosa produce lethal infections. Transcriptional profiling leads to definition of a 20-gene signature that discriminates between tolerant and susceptible states, as well as identification of a more active tolerance response to gram negative compared to gram positive bacteria. Gene pathways associated with active tolerance in Xenopus, including some involved in metal ion binding and hypoxia, are found to be conserved across species, including mammals, and administration of a metal chelator (deferoxamine) or a HIF-1α agonist (1,4-DPCA) in embryos infected with lethal A. hydrophila increased survival despite high pathogen load. These data demonstrate the value of combining the Xenopus embryo infection model with computational multiomics analyses for mechanistic discovery and drug repurposing to induce host tolerance to bacterial infections.

| S-EPMC9475558 | biostudies-literature

Development of computational approaches for cell hashing in scRNA-seq

Project description:Development of computational approaches for cell hashing in scRNA-seq

| PRJNA781338 | ENA

Development of computational approaches for cell hashing in scRNA-seq

Project description:Development of computational approaches for cell hashing in scRNA-seq

| PRJNA781337 | ENA

Anticancer metabolites discovered by Computational Metabolomics

Project description:CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. Nine metabolites predicted to be lowered in Jurkat cells with respect to normal lymphoblasts were examined: riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, α-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole. All, alone or in combination, exhibited antiproliferative activity. Of eleven metabolites predicted to be increased or unchanged in Jurkat cells, only two (bilirubin and androsterone) exhibited significant antiproliferative activity. These results suggest that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, resulting in uninhibited cellular growth and have the implication that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery. Keywords: cell type

2008-08-04 | GSE9648 | GEO

Novel integrated computational AMP discovery approaches highlight diversity in the helminth AMP repertoire

Project description:Invertebrate antimicrobial peptides (AMPs) form the first line of defence against pathogenic microbes. Understanding AMP profiles in helminths, their importance to helminth biology, and how they shape microbial communities could reveal novel approaches for anthelmintic and/or antimicrobial development. In this study, we employed a LC-MS/MS peptidomics pipeline to validate a novel integrated homology- and computational-based pipeline for the discovery of helminth AMPs. Our peptidomics pipeline found 60 high-confidence PSMs correlating to 15 high-confidence novel AMP-LPs within Ascaris suum body-cavity fluid supporting the need for further characterisation of these peptides and their functions within helminths.

2023-07-26 | PXD042293 | Pride

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