Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Small RNA-Seq of plasma-derived exosomes from Acute Respiratory Distress Syndrome patients and healthy subjects

ABSTRACT: Despite a significant progress in the treatment of Acute Respiratory Distress Syndrome (ARDS), our ability to identify early patients and predict outcome remains limited. In this study, we aimed to characterize small RNA content of plasma exosomes from ARDS patients in order to identify potential diagnostic biomarkers of the disease. For the first time, we profiled miRNA expression levels in plasma-derived exosomes from ARDS patients (n=8) compared to healthy subjects (n=10) by small RNA-seq. It allowed us to identify 12 exosomal miRNAs differentially expressed in ARDS context (padj<0.05).

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Makon-Sébastien Njock

PROVIDER: E-MTAB-9991 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AM) and peripheral blood monocytes (PBM) from patients with acute respiratory distress (ARDS) could clarify the biologic programs activated in ARDS and the relationship of these changes to clinical outcomes. Objectives: To identify transcriptional programs activated in purified AM and PBM over the course of ARDS, and determine the relationship of these programs with patient outcomes. Methods: We performed transcriptional profiling of total RNA isolated from AMs and PBMs purified from bronchoalveolar lavage fluid (BALF) and peripheral blood respectively, collected from patients (n = 26) with ARDS previously enrolled in a phase-II clinical trial. Cells were obtained at baseline (day 0) after enrollment. Measurements and Main Results: Using an unbiased gene set enrichment analysis (GSEA), we found highly divergent patterns of gene expression in AMs and PBMs. Notably, immuno-inflammatory gene sets were enriched in AMs isolated on day 0 in those who survived and had more ventilator-free days (VFD); however, this association between inflammatory and immune gene sets and good outcomes was not seen in PBMs. Conclusion: Transcriptional responses during ARDS are remarkably different between AMs and PBMs. Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AM) and peripheral blood monocytes (PBM) from patients with acute respiratory distress (ARDS) could clarify the biologic programs activated in ARDS and the relationship of these changes to clinical outcomes. Objectives: To identify transcriptional programs activated in purified AM and PBM over the course of ARDS, and determine the relationship of these programs with patient outcomes. Methods: We performed transcriptional profiling of total RNA isolated from AMs and PBMs purified from bronchoalveolar lavage fluid and peripheral blood respectively, collected from patients (n = 26) with ARDS previously enrolled in a phase-II clinical trial. Cells were obtained at baseline (day 0) after enrollment. Measurements and Main Results: Using an unbiased gene set enrichment analysis (GSEA), we found highly divergent patterns of gene expression in AMs and PBMs. Notably, immuno-inflammatory gene sets were enriched in AM isolated on day 0 in those who survived and had more ventilator-free days (VFD); however, this association between inflammatory and immune gene sets and good outcomes was not seen in PBMs. Conclusion: Transcriptional responses during ARDS are remarkably different between AM and PBM.

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Small RNA-Seq of plasma-derived exosomes from Acute Respiratory Distress Syndrome patients and healthy subjects

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