Effect of injury and Pseudomonas aeruginosa inoculation in Drosophila melanogaster
Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.
Sex, Time
View SamplesMonitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for medicines future. Patients with injury severe enough to develop multiple organ dysfunction syndrome (MODS) are known to have multiple immune derangements, including T-cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly-enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers a previously unavailable opportunity to discover novel leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in the T-cell, monocyte, and total leukocyte transcriptome, with only 12% of these genomic changes common to all three cell populations. T-cell-specific pathway analyses identified increased gene expression of several novel inhibitory receptors (PD-1, CD152, NRP-1, Lag3), and concomitant decreases in stimulatory receptors (CD28, CD4, IL-2Ralpha). Functional analysis of T-cells and monocytes confirmed reduced T-cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly-enriched cell populations combined with knowledge-based pathway analyses leads to the identification of novel regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell specific pathway analyses can be used to discover novel pathway alterations in human disease.
Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways.
No sample metadata fields
View SamplesOligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens. However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus (bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans.
A network-based analysis of systemic inflammation in humans.
No sample metadata fields
View Samplesexpression files supporting: Application of genome-wide expression analysis to human health and disease. PNAS
Application of genome-wide expression analysis to human health and disease.
No sample metadata fields
View SamplesNeutrophils play critical roles in modulating the immune response. However, neutrophils have a short circulating half life, are readily stimulated in vitro, and have low levels of cellular mRNA when compared to other blood leukocyte populations. All of these factors have made it difficult to evaluate neutrophils from clinical populations for molecular and functional studies.
Clinical microfluidics for neutrophil genomics and proteomics.
Specimen part, Subject
View SamplesIn this study, we examined transcriptional profiles from 3 different microarray platforms, across 103 peripheral blood samples with and without acute rejection, to find a critical gene-set for the diagnosis of acute renal rejection that matched biopsy diagnosis, irrespective of patient demographics, clinical confounders, concomitant infection, immunosuppression usage or sample processing methods. We hypothesized that changes in peripheral blood expression profiles correlate with biopsy-proven rejection, and that these changes could be used as biomarkers for the diagnosis and prediction of acute rejection.
A peripheral blood diagnostic test for acute rejection in renal transplantation.
Disease, Disease stage
View SamplesIn this study, we examined transcriptional profiles from 3 different microarray platforms, across 103 peripheral blood samples with and without acute rejection, to find a critical gene-set for the diagnosis of acute renal rejection that matched biopsy diagnosis, irrespective of patient demographics, clinical confounders, concomitant infection, immunosuppression usage or sample processing methods. We hypothesized that changes in peripheral blood expression profiles correlate with biopsy-proven rejection, and that these changes could be used as biomarkers for the diagnosis and prediction of acute rejection.
A peripheral blood diagnostic test for acute rejection in renal transplantation.
Disease, Disease stage
View SamplesHuman survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global
A genomic storm in critically injured humans.
Sex, Age, Specimen part
View SamplesBlood was sampled from severe burns patients over time as well as healthy subjects. Genome-wide expression analyses were conducted using the Affymetrix U133 plus 2.0 GeneChip.
Genomic responses in mouse models poorly mimic human inflammatory diseases.
Sex, Age, Specimen part
View SamplesTo understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury.
Analysis of factorial time-course microarrays with application to a clinical study of burn injury.
Sex, Disease
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