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GSE74224
Homo sapiens
105 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Background: Systemic inflammation is a whole body reaction that can have an infection-positive (i.e. sepsis) or infection-negative origin. It is important to distinguish between septic and non-septic presentations early and reliably, because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on a small number of RNAs expressed in peripheral blood could be discovered that would: 1) determine which patients with systemic inflammation had sepsis; 2) be robust across independent patient cohorts; 3) be insensitive to disease severity; and 4) provide diagnostic utility. The overall goal of this study was to identify and validate such a molecular classifier. Methods and Findings: We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICU). Biomarker discovery was conducted with an Australian cohort (n = 105) consisting of sepsis patients and post -surgical patients with infection-negative systemic inflammation. Using this cohort, a four-gene classifier consisting of a combination of CEACAM4, LAMP1, PLA2G7 and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte Lab, was externally validated using RT-qPCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Cohort 1 (n=59) consisted of unambiguous septic cases and infection-negative systemic inflammation controls; SeptiCyte Lab gave an area under curve (AUC) of 0.96 (95% CI: 0.91-1.00). ROC analysis of a more heterogeneous group of patients (Cohorts 2-5; 249 patients after excluding 37 patients with infection likelihood possible) gave an AUC of 0.89 (95% CI: 0.85-0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or the Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility o f SeptiCyte Lab was evaluated by comparison to various clinical and laboratory parameters that would be available to a clinician within 24 hours of ICU admission. SeptiCyte Lab was significantly better at differentiating sepsis from infection-negative systemic inflammation than all tested parameters, both singly and in various logistic combinations. SeptiCyte Lab more than halved the diagnostic error rate compared to PCT in all tested cohorts or cohort combinations. Conclusions: SeptiCyte Lab is a rapid molecular assay that may be clinically useful in the management of ICU patients with systemic inflammation.
Publication Title
A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 112 Downloadable Samples
NextSeq 550
Description
Predicting the impact of cis-regulatory sequence on gene expression is a foundational challenge for biology. We combine polysome profiling of hundreds of thousands of randomized 5' UTRs with deep learning to build a predictive model that relates human 5' UTR sequence to translation. Together with a genetic algorithm, we use the model to engineer new 5? UTRs that accurately target specified levels of ribosome loading, providing the ability to tune sequences for optimal protein expression. We show that the same approach can be extended to chemically modified RNA, an important feature for applications in mRNA therapeutics and synthetic biology. We test 35,000 truncated human 5' UTRs and 3,577 naturally-occurring variants and show that the model accurately predicts ribosome loading of these sequences. Finally, we provide evidence of 47 SNVs associated with human diseases that cause a significant change in ribosome loading and thus a plausible molecular basis for disease. Overall design: Polysom profiling and sequencing was performed using a library of 300,000 randomized 5' UTR 50-mers with eGFP used as the CDS. Three RNA chemistries were tested: unmodified, pseudouridine, and 1-methylpseudouridine. These were performed in duplicate (6 samples total). A designed library that includes human 5' UTRs, SNVs, and sequences engineered with a genetic algorithm was used with the eGFP CDS (no duplicate). A second randomized library used mCherry as the CDS, also performed in duplicate.
Publication Title
Human 5' UTR design and variant effect prediction from a massively parallel translation assay.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 88 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
We performed systems analyses of immune responses to the meningococcal polysaccharide (MPSV4) and conjugate (MCV4) vaccines in healthy adults.
Publication Title
Molecular signatures of antibody responses derived from a systems biology study of five human vaccines.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 232 Downloadable Samples
- IlluminaHiSeq2000
Description
Immunity to malaria can be acquired through natural exposure to Plasmodium falciparum (Pf), but only after years of repeated infections. Typically, this immunity is acquired by adolescence and confers protection against disease, but not Pf infection per se. Efforts to understand the mechanisms of this immunity are integral to the development of a vaccine that would mimic the induction of adult immunity in children. The current study applies transcriptomic analyses to a cohort from the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural Pf infection. The resulting datasets will be of considerable value in the urgent worldwide effort to develop a malaria vaccine that could prevent more than a million deaths annually. Overall design: 108 samples; paired pre- and post-challenge for 54 individuals 198 samples; paired pre- and post-challenge for 99 individuals
Publication Title
Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 693 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 621 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The objective of this study is to: 1) Characterize the immune responsiveness to administration of non-live vaccines in three cohorts of healthy adult subjects through the analysis of blood leukocytes transcriptional profiles. 2) Validate whole blood transcriptional profiles generated from standard 3mL blood draws versus 200uL blood draws obtained by finger stick. 3) Discover potential biomarkers for immune-responsiveness to non-live vaccines.
Publication Title
Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The objective of this study is to: 1) Characterize the cellular origin of transciptional signatures observed on day 1 after vaccination with 2009/10 seasonal influenza and pneumococcal vaccine discovered by transcriptional profiling of whole blood samples in data set WholeBlood_SysVax. 2) Discover potential biomarkers for immune-responsiveness to non-live vaccines.
Publication Title
Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Publication Title
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Sample Metadata Fields
Subject
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The H4K16 acetyltransferase MOF plays a crucial role in dosage compensation in Drosophila, but has additional, global functions in gene control. We compared the molecular context and effect of MOF activity in male and female flies combining chromosome-wide mapping and transcriptome studies with analyses of defined reporter loci in transgenic flies. MOF distributes dynamically between two types of complexes, the Dosage Compensation Complex (DCC) and complexes containing MBD-R2, a global facilitator of transcription. These different targeting principles define the distribution of MOF between the X chromosome and autosomes and at transcription units with 5 or 3 enrichment.
Publication Title
The activation potential of MOF is constrained for dosage compensation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
On triggering of the T cell receptor CD8 T lymphocytes downregulate expression of the transcription factor KLF2. KLF2 expression remains low as these cells differentiate to Cytotoxic T lymphocytes (CTL) but may be re-expressed depending on the local environmental signals.
Publication Title
The impact of KLF2 modulation on the transcriptional program and function of CD8 T cells.
Sample Metadata Fields
Specimen part
View Samples