Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1004025 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25617251_1.fastq.gz | Fastqsanger.gz | |||
| SRR25617251_2.fastq.gz | Fastqsanger.gz | |||
| SRR25617252_1.fastq.gz | Fastqsanger.gz | |||
| SRR25617252_2.fastq.gz | Fastqsanger.gz | |||
| SRR25617253_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:We performed an untargeted metabolomics analysis on plasma of three animal cohorts. 1) Control rats, 2) Toxins-treated rats (model of the Gulf War Syndrome), and 3) toxins-treated rats+(-)-epicatechin (Flavanol). Metabolites were extracted with ethanol:methanol (50:50) and data acquired by LC-MS/MS (Eksigent nanoLC 400 system -TripleTOF 5600, AB Sciex).
2020-09-10 | MSV000086118 | MassIVE
Project description:<p>We have used a "chemistry first" approach to discover druggable acquired vulnerabilities that arised in the pathogenesis of non-small cell lung cancer (NSCLC). We screened chemical libraries (~200,000 compounds) for chemical toxins that killed subsets of NSCLC but not normal human lung epithelial cells (HBECs). We first screened a panel of 12 NSCLC lines that represented a variety of known oncogenotypes and identified chemicals with large Z scores and appropriate properties including re-supply, chemistry, and reproducible drug response phenotypes. This was then narrowed down to a list of 202 chemicals and 18 drugs with known targeting (henceforth called "Precision Oncology Probe Set", or POPS). These, and a panel of 30 clinically available drugs, targeted therapies, and drug combinations, already in use or in trials for NSCLC treatment, were then tested on a panel of 96 NSCLC lines for their drug response phenotypes in 12-point dose response curves. This information was analyzed using scanning ranked KS (Kolmogorov-Smirnov) and elastic net biostatistics approaches to identify molecular biomarkers (mutations, mRNA expression, copy number variation, protein expression, and metabolomics) which could predict for sensitivity or resistance to a particular chemical toxin or treatment regimen. From this we have discovered that: our approach identifies already known molecular biomarker of drug sensitivities (e.g. EGFR mutations and EGFR TK inhibitors); many clinically available chemotherapy agents have molecular biomarkers predicting preclinical model drug responses; the POP set of chemical toxins provides novel drug response phenotype patterns in the large NSCLC panel different from those found with clinically available agents including a therapeutic window; many of the POP toxins only hit a small percentage (~5%) of the NSCLC panel but the POP set as a whole provides "coverage" of the entire NSCLC panel; there are simple, one or 2 component molecular biomarkers (mutations, mRNA expression) that predict responses to the different chemical toxins in the NSCLC panel; and that the molecular biomarkers provide some information on the targets and pathways involved in response to the chemical toxins. Thus, we have identified a group of chemical toxins with selectivity for subsets of NSCLC and associated tumor molecular biomarkers to facilitate their development for precision medicine, and also, in some cases, information on the targets and pathways interdicted by these chemical compounds. In addition, we have discovered NSCLC predictive biomarkers for clinically available agents.</p>
| phs001823 | dbGaP
Project description:We performed an untargeted metabolomics analysis on plasma of three animal cohorts. 1) Control rats, 2) Toxins-treated rats (model of the Gulf War Syndrome), and 3) toxins-treated rats+(-)-epicatechin (Flavanol). Metabolites were extracted with ethanol:methanol (50:50) and data acquired by LC-MS/MS (Eksigent nanoLC 400 system -TripleTOF 5600, AB Sciex).
| MSV000086118 | GNPS
Project description:The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease influenced human evolution, we studied changes in human expression of anthrax toxin receptor 2 (ANTXR2), which encodes a cell surface protein necessary for Bacillus anthracis virulence toxins to cause anthrax disease. In immune cells, ANTXR2 was 8-fold down-regulated in all available human samples compared to non-human primates, indicating regulatory changes early in the evolution of modern humans. We also observed multiple genetic signatures consistent with recent positive selection driving a European-specific decrease in ANTXR2 expression in several non-immune tissues affected by anthrax toxins. Our observations fit a model in which humans adapted to anthrax disease following early ecological changes associated with hunting and scavenging, as well as a second period of adaptation after the rise of modern agriculture.
2020-08-14 | GSE156161 | GEO
Project description:Bacillus thuringiensis israelensis (Bti) toxins are increasingly used for mosquito control, but little is known about the precise mode of action of each of these toxins, and how they interact to kill mosquito larvae. By using RNA sequencing, we investigated change in gene transcription level and polymorphismvariations associatedwith resistance to each Bti Cry toxin and to the full Bti toxin mixture in the dengue vector Aedes aegypti. The upregulation of genes related to chitin metabolismin all selected strain suggests a generalist, non-toxin-specific response to Bti selection in Aedes aegypti. Changes in the transcription level and/or protein sequences of several putative Cry toxin receptors (APNs, ALPs, α-amylases, glucoside hydrolases, ABC transporters) were specific to each Cry toxin. Selective sweeps associated with Cry4Aa resistancewere detected in 2 ALP and 1 APNgenes. The lack of selection of toxin-specific receptors in the Bti-selected strain supports the hypothesis that Cyt toxin acts as a receptor for Cry toxins in mosquitoes.
2019-05-16 | E-MTAB-7970 | biostudies-arrayexpress
Project description:Poliquin2013 - Energy Deregulations in
Parkinson's Disease
Encoded non-curated model. Issues:
- Fluxes, reactions, parameters and species properly encoded
but Figure 2 not successfully simulated.
- Unpaired values in Table 5 and Matlab Code (S5 and S6
Supplementary Material): Vm_ldh_r, Vm_t_lac, Km_ldh_nadh, Vm_cdh,
Vm_cd, Vm_fh, Cm_ldh_f,Vm_sdh and Vm_pdh
- Confusing parameter t2 on unitpulseSB; is it T_p_off or
(T_p_off + T_p_on)?
This model is described in the article:
Metabolomics and in-silico
analysis reveal critical energy deregulations in animal models
of Parkinson's disease.
Poliquin PO, Chen J, Cloutier M,
Trudeau LÉ, Jolicoeur M.
PLoS ONE 2013; 8(7): e69146
Abstract:
Parkinson's disease (PD) is a multifactorial disease known
to result from a variety of factors. Although age is the
principal risk factor, other etiological mechanisms have been
identified, including gene mutations and exposure to toxins.
Deregulation of energy metabolism, mostly through the loss of
complex I efficiency, is involved in disease progression in
both the genetic and sporadic forms of the disease. In this
study, we investigated energy deregulation in the cerebral
tissue of animal models (genetic and toxin induced) of PD using
an approach that combines metabolomics and mathematical
modelling. In a first step, quantitative measurements of
energy-related metabolites in mouse brain slices revealed most
affected pathways. A genetic model of PD, the Park2 knockout,
was compared to the effect of CCCP, a complex I blocker. Model
simulated and experimental results revealed a significant and
sustained decrease in ATP after CCCP exposure, but not in the
genetic mice model. In support to data analysis, a mathematical
model of the relevant metabolic pathways was developed and
calibrated onto experimental data. In this work, we show that a
short-term stress response in nucleotide scavenging is most
probably induced by the toxin exposure. In turn, the robustness
of energy-related pathways in the model explains how genetic
perturbations, at least in young animals, are not sufficient to
induce significant changes at the metabolite level.
This model is hosted on
BioModels Database
and identified by:
MODEL1410060000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2015-02-25 | MODEL1410060000 | BioModels
Project description:Vibrio vulnificus is an foodborne pathogen that can cause gastroenteritis and septicemia in humans. V. vulnificus secretes a multifunctional autoprocessing repeats-in-toxin (MARTX) toxin as an essential virulence factor to cause disease. MARTX toxins are pore-forming toxins that translocate multiple functionally independent effector domains into a target cell. MARTX toxins of V. vulnificus can contain anywhere from 3 to 5 of the 10 identified effector domains and strains with different effector repertories having varying virulence potential. The goal of this study was to compare how different effector combinations from an F-type MARTX toxin differentially remodel the transcriptional response of human intestinal epithelial cells (IECs). F-type MARTX toxins contain five effector domains – the actin crosslinking domain (ACD), two copies the makes caterpillar floppy-like domain (MCF), and alpha-beta hydrolase (ABH) domain, and the Ras/Rap1 specific endopeptidase (RRSP). Cultured human IECs were treated with V. vulnificus or strains modified to secrete a toxin with only ACD, ACD with MCF-ABH, ACD with RRSP, or no active effectors. We demonstrate that when no active effectors are present, the bacterium induces minimal changes in the transcriptional profile of IECs. However, the strains containing different effector combinations each uniquely remodeled the transcriptional profile of IECs. These data provide insight into how V. vulnificus strains with varying effector combinations can differentially regulate the host cell response to cause disease.
2021-11-21 | GSE189194 | GEO
Project description:Staphylococcus aureus, a gram-positive bacterium, causes food poisoning and toxic shock syndrome through the production of superantigenic toxins known as Staphylococcal enterotoxins serotypes A-J (SEA, SEB, etc.) and toxic shock syndrome toxin-1 (TSST-1). A subset of these toxins have been classified as potential biothreat agents. The chronology of molecular events that could potentially characterize superantigenic toxicity and early pathogenesis is not well understood. The focus of this study was to determine the distinct and shared mechanisms of response to three toxins of the superantigenic family, namely SEA, SEB and TSST-1. Since skin functions as the front line of the host’s defense mechanism, melanocytes were selected for the study and treated with 25 µg/mL of one of these three toxins. Cells were collected after treatment for six different time periods, ranging from 0.5 h to 48 h. Total RNA was investigated using gene expression microarrays containing approximately 50,000 probes, and a subset of the results were validated using NanoString assays. Transcriptomic expression data indicated that each of these three toxins had a unique longitudinal trajectory. In particular, the gene expression profiles of SEB post-exposure was very distinct from those for SEA and TSST-1 superantigens. All three superantigens showed enriched biological networks related to necrosis, skin disorders, and inflammation. The three superantigens share some similarities in acting on the mechanisms underlying apoptosis, innate immunity, and other biological processes. Pathways related to innate immunity, such as the patterns of cytokine production and acute-phase response, showed toxin-specific regulation. The differentially regulated networks can be logical targets for early therapeutic intervention and can potentially serve as early diagnostic markers for superantigen-induced toxicity.
2022-06-30 | GSE124756 | GEO
Project description:Virulence of many bacterial pathogens, including the important human pathogen Staphylococcus aureus, depends on the secretion of frequently high amounts of toxins. Toxin production involves the need for the bacteria to make physiological adjustments for energy conservation. While toxins are primarily known to be targets of gene regulation, such changes may be accomplished by regulatory functions of the toxins themselves. However, mechanisms by which toxins regulate gene expression have remained poorly understood. We show here that the phenol-soluble modulin toxins have gene regulatory functions, which in particular include regulation of their own export by direct interference with a GntR-type repressor protein. This capacity was most pronounced in PSMs with low cytolytic capacity, demonstrating functional specification among closely related members of that toxin family. Our study presents a paradigmatic example of how bacterial toxins may regulate gene expression to adapt to the physiological needs in situations of enhanced toxin production.
2016-12-19 | GSE72878 | GEO