03ef9418-f6cf-43ac-86b5-ab3eb8791b88 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001004488 | EGA |
REPOSITORIES: EGA
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Project description:In an endotoxaemic mouse model of sepsis, a tissue-based proteomics approach for biomarker discovery identified long pentraxin 3 (PTX3) as the lead candidate for inflamed myocardium. PTX3 accumulated as an octamer due to disulphide-bond formation in heart, kidney and lung ?common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in the circulation. The redox-state of PTX3 was quantified over the first 11 days in critically ill adult patients with sepsis. On admission day, there was no difference in the redox-state of PTX3 between survivors and non-survivors. From day 2 onwards, the conversion of octameric to monomeric PTX3 was consistently associated with a greater survival after 28 days of follow-up. For example, by day 2 post admission, octameric PTX3 was undetectable in survivors, but still constituted more than half of total PTX3 in non-survivors (P<0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP, high sensitivity troponin I and T. In comparison to the conventional measurements of total PTX3 or NT-proBNP, the redox-sensitive oligomerization of PTX3 was more dynamic and a superior predictor of disease outcome.
2014-07-01 | PXD001020 | Pride
Project description:In an endotoxaemic mouse model of sepsis, a tissue-based proteomics approach for biomarker discovery identified long pentraxin 3 (PTX3) as the lead candidate for inflamed myocardium. PTX3 accumulated as an octamer due to disulphide-bond formation in heart, kidney and lung ?common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in the circulation. The redox-state of PTX3 was quantified over the first 11 days in critically ill adult patients with sepsis. On admission day, there was no difference in the redox-state of PTX3 between survivors and non-survivors. From day 2 onwards, the conversion of octameric to monomeric PTX3 was consistently associated with a greater survival after 28 days of follow-up. For example, by day 2 post admission, octameric PTX3 was undetectable in survivors, but still constituted more than half of total PTX3 in non-survivors (P<0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP, high sensitivity troponin I and T. In comparison to the conventional measurements of total PTX3 or NT-proBNP, the redox-sensitive oligomerization of PTX3 was more dynamic and a superior predictor of disease outcome.
2017-11-10 | MSV000081708 | MassIVE
Project description:1364 plasma proteome samples taken at time-of-admission to the emergency department from patients suspected of sepsis.
Used initially with the following abstract:
Sepsis is one of the leading causes of mortality in the world. Currently, the heterogeneity of sepsis makes it challenging to determine the molecular mechanisms that define the syndrome. Here, we leverage population scale proteomics to analyze a well-defined cohort of 1364 blood samples taken at time-of-admission to the emergency department from patients suspected of sepsis. We identified panels of proteins using explainable artificial intelligence that predict clinical outcomes and applied these panels to reduce high-dimensional proteomics data to a low-dimensional interpretable latent space (ILS). Using the ILS, we constructed an adaptive digital twin model that accurately predicted organ dysfunction, mortality, and early-mortality-risk patients using only data available at time-of-admission. In addition to being highly effective for investigating sepsis, this approach supports the flexible incorporation of new data and can generalize to other diseases to aid in translational research and the development of precision medicine.
2024-04-08 | MSV000094486 | MassIVE
Project description:Purpose: A method for mapping chromatin accessibility genome-wide, to reveal chromatin accessibility in Intestinal stem cells. Methods: Intestinal stem cells(Lgr5-high cells) were sorted by flow cytometry from wild type mice. The samples were prepared in duplicate. HISAT2 was used to align the sequences to the mouse genome and generate bam files. bamCoverage was used to generate bigwig files from bam files. MACS2 (v2.2.5) was used for peak calling and to generate bed files from aligned reads. Conclusions: ATAC-seq analysis confirmed that Fosb binding sites in Chip-seq assay were correlated with the chromatin accessibility .
2023-04-13 | GSE186916 | GEO
Project description:The number of organ failures at intensive care unit (ICU) admission is the main prognostic factor in septic shock. The aim was to assess classical clinico-biological parameters evaluating organ dysfunctions at ICU admission, combined with proteomics analysis, on day-30 mortality in critically ill onco-hematology patients admitted to the ICU for septic shock.
2018-08-22 | PXD004001 | Pride
Project description:<p><strong>BACKGROUND:</strong> There is a critical need for rapid viral infection diagnostics to enable prompt case identification in pandemic settings and support targeted antimicrobial prescribing.</p><p><strong>METHODS:</strong> Using untargeted high-resolution liquid chromatography coupled with mass spectrometry, we compared the admission serum metabolome of emergency department patients with acute viral infections, including COVID-19, bacterial infections, inflammatory conditions and healthy controls. Sera from an independent cohort of emergency department patients admitted with viral or bacterial infections underwent profiling to validate findings. Associations between whole-blood gene expression and the identified metabolite of interest were examined.</p><p><strong>FINDINGS:</strong> 3'-Deoxy-3',4'-didehydro-cytidine (ddhC), a free base of the only known human antiviral small molecule ddhC-triphosphate (ddhCTP), was detected for the first time in serum. When comparing 60 viral with 101 non-viral cases in the discovery cohort, ddhC was the most differentially abundant metabolite, generating an area under the receiver operating characteristic curve (AUC) of 0.954 (95% CI: 0.923-0.986). In the validation cohort, ddhC was again the most significantly differentially abundant metabolite when comparing 40 viral with 40 bacterial cases, generating an AUC of 0.81 (95% CI: 0.708-0.915). Transcripts of viperin and <em>CMPK2</em>, enzymes responsible for ddhCTP synthesis, were amongst the 5 genes most highly correlated with ddhC abundance.</p><p><strong>CONCLUSIONS: </strong>The antiviral precursor molecule ddhC is detectable in serum and an accurate marker for acute viral infection. Interferon-inducible genes, viperin and <em>CMPK2</em> are implicated in ddhC production <em>in vivo</em>. These findings highlight a future diagnostic role for ddhC in viral diagnosis, pandemic preparedness and acute infection management.</p><p><strong>FUNDING:</strong> National Institute for Health Research Imperial Biomedical Research Centre; Medical Research Council.</p>
2022-02-10 | MTBLS718 | MetaboLights
Project description:Background: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). Aims: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. Methods: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurologically favorable outcome (Cerebral Performance Category [CPC] = 1-2) vs unfavorable outcome (CPC>2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. Results: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (Specificity=88%; Hit Rate=83%). Conclusions: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.
2019-03-21 | E-MTAB-7699 | biostudies-arrayexpress