title: Gene networks in skeletal muscle following endurance exercise are coexpressed in blood neutrophils and linked with blood inflammation markers.
abstract: It remains incompletely understood whether there is an association between the transcriptome profiles of skeletal muscle and blood leukocytes in response to exercise or other physiological stressors. We have previously analyzed the changes in the muscle and blood neutrophil transcriptome in eight trained men before and 3, 48, and 96 h after 2 h cycling and running. Because we collected muscle and blood in the same individuals and under the same conditions, we were able to directly compare gene expression between the muscle and blood neutrophils. Applying weighted gene coexpression network analysis (WGCNA) as an advanced network-driven method to these original data sets enabled us to compare the muscle and neutrophil transcriptomes in a rigorous and systematic manner. Two gene networks were identified that were preserved between skeletal muscle and blood neutrophils, functionally related to mitochondria and posttranslational processes. Strong preservation measures (Zsummary> 10) for both muscle-neutrophil gene networks were evident within the postexercise recovery period. Muscle and neutrophil gene coexpression was strongly correlated in the mitochondria-related network (r= 0.97;P= 3.17E-2). We also identified multiple correlations between muscular gene subnetworks and exercise-induced changes in blood leukocyte counts, inflammation, and muscle damage markers. These data reveal previously unidentified gene coexpression between skeletal muscle and blood neutrophils following exercise, showing the value of WGCNA to understand exercise physiology. Furthermore, these findings provide preliminary evidence in support of the notion that blood neutrophil gene networks may potentially help us to track physiological and pathophysiological changes in the muscle.NEW & NOTEWORTHYBy using weighted gene coexpression network analysis, an advanced bioinformatics method, we have identified previously unknown, functional gene networks that are preserved between skeletal muscle and blood neutrophils during recovery from exercise. These novel preliminary data suggest that muscular gene networks are coexpressed in blood leukocytes following physiological stress. This is a step forward toward the development of blood neutrophil gene subnetworks as part of blood biomarker panels to assess muscle health and disease.
authors.affiliation: Tissue Repair and Translational Physiology Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Broadbent
authors.affiliation: Tissue Repair and Translational Physiology Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Dayle
authors.initials: D
authors.lastname: Sampson
authors.affiliation: School of Allied Health Sciences, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors.forename: Surendran
authors.identifier: http://orcid.org/0000-0003-1267-6035
authors.initials: S
authors.lastname: Sabapathy
authors.affiliation: School of Allied Health Sciences, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Haseler
authors.affiliation: Department of Nutritional Sciences, Faculty of Life Sciences and Research Platform Active Ageing, University of Vienna, Vienna, Austria; and.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wagner
authors.affiliation: School of Medical Science, Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors.forename: Andrew C
authors.identifier: http://orcid.org/0000-0002-2994-7893
authors.initials: AC
authors.lastname: Bulmer
authors.affiliation: Tissue Repair and Translational Physiology Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Peake
authors.affiliation: Tissue Repair and Translational Physiology Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; oliver.neubauer@qut.edu.au.
authors.forename: Oliver
authors.identifier: http://orcid.org/0000-0001-6835-8787
authors.initials: O
authors.lastname: Neubauer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015444:Exercise / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007958:Leukocyte Count / Q000379:methods; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology*; D012420:Running / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology; D059467:Transcriptome / Q000502:physiology
chemical_list: D015415:Biomarkers
keywords: biomarker discovery; muscle transcriptome; network biology; neutrophil transcriptome; physiological stress