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Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome

Overview
Description:

CAP-Sys

Programme: This Project is not associated with a Programme

LHA-ID: 7RU79AQTHH-3

Funding codes:
  • German Federal Ministry of Education and Science (BMBF grant 01ZX1304A)

Public web page: Not specified

Human Diseases: Disease by infectious agent

Leipzig Health Atlas PALs: Hans Binder

Project Coordinators: No Project coordinators for this Project

Project start date: 1st Jan 2017

Project Hierarchy

Related items

Hans Binder palproject_administrator

Projects: Leipzig Melanoma Studies, Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome

Institutions: Interdisciplinary Center for Bioinformatics

https://orcid.org/0000-0002-2242-4678
Lydia Hopp asset_housekeeperasset_gatekeeper

Projects: Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome

Institutions: Interdisciplinary Center for Bioinformatics

René Hänsel adminproject_administratorasset_housekeeperasset_gatekeeperprogramme_administrator

Projects: Leipzig Health Atlas, LIFE Adult, LIFE- Leipzig Research Center for Civilization Diseases, LIFE Head and Neck Cancer Group, Onto-Med Research Group, LIFE Heart, Molecular mechanisms in malignant lymphoma, German Lymphoma Alliance (GLA), Molecular Mechanisms in Malignant Lymphomas - Demonstrators of Personalized Medicine, Individualized model-based managing of the next-cycle thrombopenia of CHOEP/CHOP treated patients based on platelets dynamics during the previous cycles, German Consortium for Hereditary Breast and Ovarian Cancer, German Consortium for Hereditary Non-Polyposis Colorectal Cancer, MMML-MYC-SYS, Natural Language Processing for Clinical Research, Genetical Statistics and Systems Biology, German Competence Network Sepsis (SepNet), LIFE Child, Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome, Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome, ProstataCA

Institutions: Institute for Medical Informatics, Statistics and Epidemiology

https://orcid.org/0000-0001-8344-0658
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Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome.
Footprints of Sepsis Framed Within Community Acquired Pneumonia in the Blood Transcriptome

Abstract (Expand)

We analyzed the blood transcriptome of sepsis framed within community-acquired pneumonia (CAP) and characterized its molecular and cellular heterogeneity in terms of functional modules of co-regulated … genes with impact for the underlying pathophysiological mechanisms. Our results showed that CAP severity is associated with immune suppression owing to T-cell exhaustion and HLA and chemokine receptor deactivation, endotoxin tolerance, macrophage polarization, and metabolic conversion from oxidative phosphorylation to glycolysis. We also found footprints of host's response to viruses and bacteria, altered levels of mRNA from erythrocytes and platelets indicating coagulopathy that parallel severity of sepsis and survival. Finally, our data demonstrated chromatin re-modeling associated with extensive transcriptional deregulation of chromatin modifying enzymes, which suggests the extensive changes of DNA methylation with potential impact for marker selection and functional characterization. Based on the molecular footprints identified, we propose a novel stratification of CAP cases into six groups differing in the transcriptomic scores of CAP severity, interferon response, and erythrocyte mRNA expression with impact for prognosis. Our analysis increases the resolution of transcriptomic footprints of CAP and reveals opportunities for selecting sets of transcriptomic markers with impact for translation of omics research in terms of patient stratification schemes and sets of signature genes.

Authors: Lydia Hopp, Henry Löffler-Wirth, L. Nersisyan, A. Arakelyan, Hans Binder

Date Published: 2nd Aug 2018

Journal: Front Immunol

Human Diseases: disease by infectious agent, pneumonia

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