title: Multiplex matrix network analysis of protein complexes in the human TCR signalosome.
abstract: Multiprotein complexes transduce cellular signals through extensive interaction networks, but the ability to analyze these networks in cells from small clinical biopsies is limited. To address this, we applied an adaptable multiplex matrix system to physiologically relevant signaling protein complexes isolated from a cell line or from human patient samples. Focusing on the proximal T cell receptor (TCR) signalosome, we assessed 210 pairs of PiSCES (proteins in shared complexes detected by exposed surface epitopes). Upon stimulation of Jurkat cells with superantigen-loaded antigen-presenting cells, this system produced high-dimensional data that enabled visualization of network activity. A comprehensive analysis platform generated PiSCES biosignatures by applying unsupervised hierarchical clustering, principal component analysis, an adaptive nonparametric with empirical cutoff analysis, and weighted correlation network analysis. We generated PiSCES biosignatures from 4-mm skin punch biopsies from control patients or patients with the autoimmune skin disease alopecia areata. This analysis distinguished disease patients from the controls, detected enhanced basal TCR signaling in the autoimmune patients, and identified a potential signaling network signature that may be indicative of disease. Thus, generation of PiSCES biosignatures represents an approach that can provide information about the activity of protein signaling networks in samples including low-abundance primary cells from clinical biopsies.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Stephen E P
authors.initials: SE
authors.lastname: Smith
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Neier
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Brendan K
authors.initials: BK
authors.lastname: Reed
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Tessa R
authors.initials: TR
authors.lastname: Davis
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Sinnwell
authors.affiliation: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.affiliation: Department of Dermatology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Gabriel F
authors.initials: GF
authors.lastname: Sciallis
authors.affiliation: Department of Dermatology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Carilyn N
authors.initials: CN
authors.lastname: Wieland
authors.affiliation: Department of Dermatology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Rochelle R
authors.initials: RR
authors.lastname: Torgerson
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Gil
authors.affiliation: University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN 55455, USA. schrum.adam@mayo.edu neuha001@umn.edu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Neuhauser
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. schrum.adam@mayo.edu neuha001@umn.edu.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Schrum
mesh_terms: D000505:Alopecia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D006801:Humans; D019169:Jurkat Cells; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D011948:Receptors, Antigen, T-Cell