A novel network approach reveals tissue-specific cellular modulators of the immune-fibrotic axis in systemic sclerosis
A novel network approach reveals tissue-specific cellular modulators of the immune-fibrotic axis in systemic sclerosis
Abstract Systems biology uses genome-scale data to determine the molecular mechanisms behind normal and disease states. We developed a novel computational method, which allowed for the first time, identification of a disease-associated signature across multiple tissues and organs in systemic sclerosis (SSc), a rare and sometimes fatal autoimmune disease. We find a common immune-fibrotic axis associated with the most severe disease phenotypes, including pulmonary fibrosis and pulmonary arterial hypertension. We evaluated disease-associated gene-gene interactions in the context of tissue-specific functional genomic networks and utilized differential network analysis to gain important insights into the role of pro-fibrotic macrophages in SSc. Using a novel cell type-aware multi-network approach, we find that genes modulated by immunosuppressive treatment occupy privileged positions in the skin-specific network. In total, this study not only presents a set of putative therapeutic targets for SSc, but a framework for multi-tissue functional genomic studies of complex human disease.
Hinchcliff Monique E.、Wood Tammara A.、Christmann Romy B.、Lafyatis Robert A.、Greene Casey S.、Mahoney J. Matthew、Farber Harrison W.、Denton Christopher P.、Whitfield Michael L.、Taroni Jaclyn N.、Martyanov Viktor、Pioli Patricia A.
Division of Rheumatology, Department of Medicine, Feinberg School of Medicine, Northwestern UniversityDepartment of Genetics, Geisel School of Medicine at DartmouthDivision of Rheumatology, Department of Medicine, Boston University School of MedicineDivision of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh Medical CenterDepartment of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of PennsylvaniaDepartment of Neurological Sciences, University of VermontPulmonary Center, Department of Medicine, Boston University School of MedicineDivision of Medicine, University College LondonDepartment of Genetics, Geisel School of Medicine at DartmouthDepartment of Genetics, Geisel School of Medicine at DartmouthDepartment of Genetics, Geisel School of Medicine at DartmouthDepartment of Obstetrics and Gynecology, Geisel School of Medicine at Dartmouth
医学研究方法基础医学内科学
Hinchcliff Monique E.,Wood Tammara A.,Christmann Romy B.,Lafyatis Robert A.,Greene Casey S.,Mahoney J. Matthew,Farber Harrison W.,Denton Christopher P.,Whitfield Michael L.,Taroni Jaclyn N.,Martyanov Viktor,Pioli Patricia A..A novel network approach reveals tissue-specific cellular modulators of the immune-fibrotic axis in systemic sclerosis[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/038950.点此复制
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