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Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis

ABSTRACT: Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis

PROVIDER: PRJNA683803 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13224400_1.fastq.gz	Fastqsanger.gz
	SRR13224400_2.fastq.gz	Fastqsanger.gz
	SRR13224500_1.fastq.gz	Fastqsanger.gz
	SRR13224500_2.fastq.gz	Fastqsanger.gz
	SRR13224600_1.fastq.gz	Fastqsanger.gz

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Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis

Project description:to identify transcriptomic biomarker pathways in peripheral blood that are associated with or predict the development of death or fatal C-IRIS among patients with CM who were enrolled in the Cryptococcal Optimal ART Timing (COAT) Trial.

2021-03-01 | GSE162914 | GEO

Expression profiles of circRNAs in peripherial blood mononuclear cells from cryptococcal meningitis and healthy individuals.

Project description:CircRNAs are a recently well-known regulator that mediates a variety of biological processes. Cryptococcus neoformans is an environmental fungal pathogen that can cause fatal cryptococcal meningitis in immunocompromised individuals. However, the involvement of circRNA in cryptococcal infection remains unclear. In this study, high‐throughput microarray was performed to identify the circRNA expression profile in cryptococcal meningitis patients.

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Project description:Single-end reads of serial isolates from cryptococcal meningitis cases

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Quantitative proteomics of cryptococcal meningitis brain tissues

Project description:Quantitative proteomics of cryptococcal meningitis brain tissues and control brain tissues was carried out to study the host factors that are activated and differentially regulated in response to infection. Proteins isolated from infected brain tissues were subjected to trypsin digestion and then labeled using 4-plex iTRAQ labels. iTRAQ labeled peptides were subjected to fractionation by SCX. All the fractions were analyzed on the high resolution Orbitrap Velos mass spectrometer.

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Gene Expression Profiling of Tuberculous Meningitis coinfected with HIV

Project description:Tuberculosis co-infected with HIV may increase the risk of causing meningitis. Tuberculous meningitis co-infected with HIV associated with high mortality and severe neurological abnormalities in affected individuals. We have carried out TBM co-infected with HIV gene expression study using whole human genome microarrays. We identified 796 differentially expressed genes with fold change cut off of 2 or more than 2. Out of 796 differentially expressed genes, 398 were upregulated and 396 were downregulated. We have validated two molecules from microarray data using immunohistochemistry. The proposed study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis coinfected with HIV and four head injury cases were used as controls. We have used 4X44K arrays from agilent platform. To validate our microarray results, we have done immunohistochemistry on 10 TBM+HIV cases and 10 control groups.

2012-12-31 | E-GEOD-29507 | biostudies-arrayexpress

Gene Expression Profiling of Tuberculous Meningitis coinfected with HIV

2012-12-31 | GSE29507 | GEO

Value of lipocalin 2 as a potential biomarker for bacterial meningitis

Project description:Objectives: Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. We aimed to discover protein biomarkers that could rapidly and accurately identify the likely cause of the infections, essential for clinical management and improving outcome. Methods: We applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in Vietnam. Results: In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis (BM) other than tuberculous meningitis. The analysis of the validation cohort showed that LCN2 could discriminate BM from other CNS infections (including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis), with the sensitivity: 0.88 (95% confident interval (CI): 0.77-0.94), the specificity: 0.91 (95%CI: 0.88-0.94) and the diagnostic odd ratio: 73.8 (95%CI: 31.8-171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2, CSF leukocytes, glucose, protein and lactate resulted in the highest diagnostic performance for BM (area under receiver-operating-characteristic-curve 0.96; 95%CI: 0.93-0.99). Conclusions: Our results suggest that LCN2 is a sensitive and specific biomarker for discriminating BM from a broad spectrum of other CNS infections. A prospective study is needed to assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections..

2020-08-20 | PXD020510 | Pride

Transcriptomic biomarker pathways associated with death in HIV-infected patients with cryptococcal meningitis.

Project description:BackgroundCryptococcal meningitis (CM) is a major cause of death in HIV-infected patients in sub-Saharan Africa. Many CM patients experience cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS), which is often fatal. We sought to identify transcriptomic biomarker pathways in peripheral blood that are associated with or predict the development of death or fatal C-IRIS among patients with CM who were enrolled in the Cryptococcal Optimal ART Timing Trial.MethodsWe assessed peripheral blood gene expression using next-generation RNA sequencing in 4 groups of patients with CM: (1) no C-IRIS or Death; (2) C-IRIS survivors; (3) fatal C-IRIS; (4) Death without C-IRIS. Gene expression was assessed at the time of ART initiation, at 1, 4, and 8 weeks on ART, and at the time of C-IRIS events.ResultsWe identified 12 inflammatory and stress response pathways, including interferon type 1 signaling, that were upregulated at the time of ART initiation in patients with future fatal C-IRIS, as compared with survivors. The upregulation of transcripts involved in innate immunity (inflammasome, Toll-like receptor signaling), was observed at the time of fatal or nonfatal C-IRIS events. At the time of fatal C-IRIS events, numerous transcripts within fMLP, Rho family GTPases, HMGB1, and other acute phase response signaling pathways were upregulated, which reflects the severity of inflammation and systemic oxidative stress. Patients who died without recognized C-IRIS also had increased expression of pathways associated with oxidative stress and tissue damage.ConclusionsOur results showed that overactivated innate immunity, involving Toll-like receptor/inflammasome pathways, and inflammation-induced oxidative stress, are associated with fatal outcomes. The results of this study provide insight into the molecular drivers of death and fatal C-IRIS to inform future diagnostic test development or guide targeted treatments.

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Blood transcriptional signature of HIV-associated tuberculous meningitis

Project description:Patients with HIV-associated TB meningitis (TBM) are known to experience systemic hyperinflammation, clinically known as immune reconstitution inflammatory syndrome (IRIS), following the commencement of antiretroviral therapy (ART). No prognostic markers or biomarkers have been identified to date and little is known about the mechanism mediating the hyperinflammation. We recruited a prospective cohort of 33 patients with HIV-associated TBM, 16 of whom developed TBM-IRIS, and performed transcriptomic profiling. Transcriptomic signatures that distinguish patients who would eventually develop IRIS were identified and indicated neutrophil and inflammasome activation as being the predominant mediator of TBM-IRIS pathogenesis.

2017-06-10 | GSE83892 | GEO

Tuberculous Meningitis in Pediatric Patients

Project description:Whole blood transcriptional profiles in children with or without tuberculous meningitis (TBM) were compared using RNA-Seq and a biomarker signature driven by inflammasome activation and signaling was identified

2019-08-06 | GSE111459 | GEO

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