title: LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.
abstract: Lipopolysaccharide (endotoxin, LPS) is a strong inducer of the innate immune response. It is widespread in our environment, e.g. in house dust and contributes to asthma. Compared to humans, horses are even more sensitive to LPS. However, data on LPS effects on the equine transcriptome are very limited. Using RNA-seq we analysed LPS-induced differences in the gene expression in equine peripheral blood mononuclear cells at the gene and gene-network level in two half-sib families and one group of unrelated horses.
  
  
  
  24 h-LPS challenge of equine immune cells resulted in substantial changes in the transcriptomic profile (1,265 differentially expressed genes) showing partial overlap with human data. One of the half-sib families showed a specific response different from the other two groups of horses. We also identified co-expressed gene modules that clearly differentiated 24 h-LPS- from non-stimulated samples. These modules consisted of 934 highly interconnected genes and included genes involved in the immune response (e.g. IL6, CCL22, CXCL6, CXCL2), however, none of the top ten hub genes of the modules have been annotated as responsive to LPS in gene ontology.
  
  
  
  Using weighted gene co-expression network analysis we identified ten co-expressed gene modules significantly regulated by in vitro stimulation with LPS. Apart from 47 genes (5%) all other genes highly interconnected within the most up- and down-regulated modules were also significantly differentially expressed (FDR < 0.05). The LPS-regulated module hub genes have not yet been described as having a role in the immune response to LPS (e.g. VAT1 and TTC25).
authors.affiliation: Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3012, Bern, Switzerland. alicja@rth.dk.|Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland. alicja@rth.dk.
authors.forename: Alicja
authors.identifier: 0000-0002-4888-4883
authors.initials: A
authors.lastname: Pacholewska
authors.affiliation: Department of Clinical Research and Veterinary Public Health, Division of Experimental Clinical Research, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, 3012, Bern, Switzerland.
authors.forename: Eliane
authors.initials: E
authors.lastname: Marti
authors.affiliation: Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland.
authors.forename: Tosso
authors.initials: T
authors.lastname: Leeb
authors.affiliation: Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Jagannathan
authors.affiliation: Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3012, Bern, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Gerber
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D000068617:Genetic Background; D006736:Horses; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D059467:Transcriptome
chemical_list: D008070:Lipopolysaccharides
keywords: Differential expression; Gene modules; Horse; LPS; Lipopolysaccharides; RNA-seq; WGCNA