Immune gene expression networks in sepsis : A network biology approach

To study the dysregulated host immune response to infection in sepsis, gene expression profiles from the Gene Expression Omnibus (GEO) datasets GSE54514, GSE57065, GSE64456, GSE95233, GSE66099 and GSE72829 were selected. From the Kyoto Encyclopedia of Genes and Genomes (KEGG) immune system pathways, 998 unique genes were selected, and genes were classified as follows based on gene annotation from KEGG, Gene Ontology, and Reactome: adaptive immunity, antigen presentation, cytokines and chemokines, complement, hematopoiesis, innate immunity, leukocyte migration, NK cell activity, platelet activity, and signaling. After correlation matrix formation, correlation coefficient of 0.8 was selected for network generation and network analysis. Total transcriptome was analyzed for differentially expressed genes (DEG), followed by gene set enrichment analysis. The network topological structure revealed that adaptive immunity tended to form a prominent and isolated cluster in sepsis. Common genes within the cluster from the 6 datasets included CD247, CD8A, ITK, LAT, and LCK. The clustering coefficient and modularity parameters were increased in 5/6 and 4/6 datasets in the sepsis group that seemed to be associated with functional aspect of the network. GSE95233 revealed that the nonsurvivor group showed a prominent and isolated adaptive immunity cluster, whereas the survivor group had isolated complement-coagulation and platelet-related clusters. T cell receptor signaling (TCR) pathway and antigen processing and presentation pathway were down-regulated in 5/6 and 4/6 datasets, respectively. Complement and coagulation, Fc gamma, epsilon related signaling pathways were up-regulated in 5/6 datasets. Altogether, network and gene set enrichment analysis showed that adaptive-immunity-related genes along with TCR pathway were down-regulated and isolated from immune the network that seemed to be associated with unfavorable prognosis. Prominence of platelet and complement-coagulation-related genes in the immune network was associated with survival in sepsis. Complement-coagulation pathway was up-regulated in the sepsis group that was associated with favorable prognosis. Network and gene set enrichment analysis supported elucidation of sepsis pathogenesis.

Errataetall:

CommentIn: Front Immunol. 2023 Nov 20;14:1286203. - PMID 38054005

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:16

Enthalten in:

PloS one - 16(2021), 3 vom: 05., Seite e0247669

Sprache:

Englisch

Beteiligte Personen:

Kim, Kyung Soo [VerfasserIn]
Jekarl, Dong Wook [VerfasserIn]
Yoo, Jaeeun [VerfasserIn]
Lee, Seungok [VerfasserIn]
Kim, Myungshin [VerfasserIn]
Kim, Yonggoo [VerfasserIn]

Links:

Volltext

Themen:

9007-36-7
Adaptor Proteins, Signal Transducing
CD3 Complex
CD3 antigen, zeta chain
CD8 Antigens
CD8 antigen, alpha chain
Complement System Proteins
EC 2.7.10.1
EC 2.7.10.2
Emt protein-tyrosine kinase
Journal Article
LAT protein, human
LCK protein, human
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
Membrane Proteins
Protein-Tyrosine Kinases
Receptors, Antigen, T-Cell
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 07.09.2021

Date Revised 27.03.2024

published: Electronic-eCollection

CommentIn: Front Immunol. 2023 Nov 20;14:1286203. - PMID 38054005

Citation Status MEDLINE

doi:

10.1371/journal.pone.0247669

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM322245265