Transcriptomics

Dataset Information

98

Integrative ‘omic analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from SIRS


ABSTRACT: Rationale: Sepsis is a leading cause of morbidity and mortality; early diagnosis and prediction of progression is difficult to determine. The integration of metabolomic and transcriptomic data in an experimental model of sepsis may be a novel method to identify molecular signatures of clinical sepsis. Objectives: Develop a biomarker panel for earlier diagnosis and prognostic characterization of sepsis patients to inform personalized clinical management and improve understanding of the pathophysiology of sepsis progression. Methods: Mild to severe sepsis, lung injury and death was recapitulated in Macaca fascicularis by intravenous inoculation of Escherichia coli. Plasma samples were obtained at time of challenge and at one, three, and five days later or time of euthanasia. Necropsy was performed and blood, lung, kidney and spleen samples were obtained. An integrative analysis of comprehensive metabolomic and transcriptomic datasets was performed to identify and parameterize a biomarker panel. Measurements and Main Results: Pathogen invasion, respiratory distress, lethargy and mortality was dose dependent. Severe infection and death were associated with metabolomic and transcriptomic changes indicative of mitochondrial, peroxisomal and liver dysfunction. Analysis of reciprocal pulmonary transcriptome and plasma metabolome data revealed an integrated host response that suggested dysregulated fatty acid catabolism resulting from peroxisome-proliferator activated receptor signaling. A representative 4-metabolite model effectively diagnosed sepsis in primates (AUC 0.966) and in two human sepsis cohorts (AUC=0.78 and 0.82). Conclusion: A model to guide early management of patients with sepsis was developed by analysis of reciprocal metabolomic and transcriptomic data in primates that diagnosed sepsis in humans. Transcriptomic analysis of lungs from Cynomolgus macaques challenged with E. coli

ORGANISM(S): Macaca fascicularis  

SUBMITTER: Shannon Bruse  Raymond J Langley    

PROVIDER: E-GEOD-59075 | ArrayExpress | 2015-08-19

SECONDARY ACCESSION(S): SRP044045GSE59075PRJNA254331

REPOSITORIES: GEO, ArrayExpress, ENA

altmetric image

Publications

Sorry, this publication's infomation has not been loaded in the Indexer, please go directly to PUBMED or Altmetric.

Similar Datasets

2016-03-16 | E-GEOD-63042 | ArrayExpress
2016-04-07 | E-GEOD-63042 | ExpressionAtlas
| GSE70714 | GEO
2017-08-23 | E-GEOD-51799 | ArrayExpress
2017-04-30 | E-MTAB-4549 | ArrayExpress
| GSE53007 | GEO
2014-11-28 | E-GEOD-63311 | ArrayExpress
| GSE92703 | GEO
2012-01-11 | E-GEOD-29188 | ArrayExpress
2014-05-03 | E-MTAB-375 | ArrayExpress