title: An Interactive Macrophage Signal Transduction Map Facilitates Comparative Analyses of High-Throughput Data.
abstract: Macrophages (Mϕs) are key players in the coordination of the lifesaving or detrimental immune response against infections. The mechanistic understanding of the functional modulation of Mϕs by pathogens and pharmaceutical interventions at the signal transduction level is still far from complete. The complexity of pathways and their cross-talk benefits from holistic computational approaches. In the present study, we reconstructed a comprehensive, validated, and annotated map of signal transduction pathways in inflammatory Mϕs based on the current literature. In a second step, we selectively expanded this curated map with database knowledge. We provide both versions to the scientific community via a Web platform that is designed to facilitate exploration and analysis of high-throughput data. The platform comes preloaded with logarithmic fold changes from 44 data sets on Mϕ stimulation. We exploited three of these data sets-human primary Mϕs infected with the common lung pathogensStreptococcus pneumoniae,Legionella pneumophila, orMycobacterium tuberculosis-in a case study to show how our map can be customized with expression data to pinpoint regulated subnetworks and druggable molecules. From the three infection scenarios, we extracted a regulatory core of 41 factors, including TNF, CCL5, CXCL10, IL-18, and IL-12 p40, and identified 140 drugs targeting 16 of them. Our approach promotes a comprehensive systems biology strategy for the exploitation of high-throughput data in the context of Mϕ signal transduction. In conclusion, we provide a set of tools to help scientists unravel details of Mϕ signaling. The interactive version of our Mϕ signal transduction map is accessible online at https://vcells.net/macrophage.
authors.affiliation: Labor für Systemtumorimmunologie, Hautklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Wentker
authors.affiliation: Labor für Systemtumorimmunologie, Hautklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Eberhardt
authors.affiliation: Labor für Systemtumorimmunologie, Hautklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
authors.forename: Florian S
authors.initials: FS
authors.lastname: Dreyer
authors.affiliation: Institute for Lung Research/iLung, German Center for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps University Marburg, 35043 Marburg, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bertrams
authors.affiliation: Labor für Systemtumorimmunologie, Hautklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, 91054 Erlangen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Cantone
authors.affiliation: Institute for Lung Research/iLung, German Center for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps University Marburg, 35043 Marburg, Germany.|Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité University Medicine Berlin, 13353 Berlin, Germany; and.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Griss
authors.affiliation: Institute for Lung Research/iLung, German Center for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps University Marburg, 35043 Marburg, Germany.|Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps University Marburg, 35043 Marburg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Schmeck
authors.affiliation: Labor für Systemtumorimmunologie, Hautklinik, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, 91054 Erlangen, Germany; julio.vera-gonzalez@uk-erlangen.de.
authors.forename: Julio
authors.identifier: 0000-0002-3076-5122
authors.initials: J
authors.lastname: Vera
mesh_terms: D019295:Computational Biology; D066264:Datasets as Topic; D053263:Gene Regulatory Networks; D057166:High-Throughput Screening Assays; D006801:Humans; D056747:Immunomodulation; D007249:Inflammation / Q000276:immunology*; D016952:Legionella pneumophila / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000276:immunology*; D015398:Signal Transduction; D012984:Software; D013296:Streptococcus pneumoniae / Q000276:immunology*; D049490:Systems Biology