Network analysis of inflammatory responses to sepsis by neutrophils and peripheral blood mononuclear cells
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Date
2018-08-07
Authors
Godini, Rasoul
Fallahi, Hossein
Ebrahimie, Esmaeil
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Rights
© 2018 Godini et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Rights Holder
© 2018 Godini et al.
Abstract
Sepsis is a life-threatening syndrome causing thousands of deaths yearly worldwide. Sepsis
is a result of infection and could lead to systemic inflammatory responses and organ failures.
Additionally, blood cells, as the main cells in the immune systems, could be also affected
by sepsis. Here, we have used different network analysis approaches, including Weighted
Gene Co-expression Network Analysis (WGCNA), Protein-Protein Interaction (PPI), and
gene regulatory network, to dissect system-level response to sepsis by the main white blood
cells. Gene expression profiles of Neutrophils (NTs), Dendritic Cells (DCs), and Peripheral
Blood Mononuclear Cells (PBMCs) that were exposed to septic plasma were obtained and
analyzed using bioinformatics approaches. Individual gene expression matrices and the list
of differentially expressed genes (DEGs) were prepared and used to construct several networks.
Consequently, key regulatory modules and hub genes were detected through network
analysis and annotated through ontology analysis extracted from DAVID database.
Our results showed that septic plasma affected the regulatory networks in NTs, PBMCs
more than the network in DCs. Gene ontology of DEGs revealed that signal transduction
and immune cells responses are the most important biological processes affected by sepsis.
On the other hand, network analysis detected modules and hub genes in each cell types. It
was found that pathways involved in immune cells, signal transduction, and apoptotic processes
are among the most affected pathways in the responses to sepsis. Altogether, we
have found several hub genes including ADORA3, CD83 CDKN1A, FFAR2, GNAQ, IL1B,
LTB, MAPK14, SAMD9L, SOCS1, and STAT1, which might specifically respond to sepsis
infection. In conclusion, our results uncovered the system-level responses of the main white
blood cells to sepsis and identified several hub genes with potential applications for therapeutic
and diagnostic purposes.
Description
This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.
Keywords
Citation
Godini, R., Fallahi, H., Ebrahimie, E., (2018). Network analysis of inflammatory responses to sepsis by neutrophils and peripheral blood mononuclear cells. PLoS ONE, 13(8): e0201674.