RT Journal Article SR Electronic T1 Extreme phenotypes define epigenetic and metabolic signatures in cardiometabolic syndrome JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.03.06.961805 DO 10.1101/2020.03.06.961805 A1 Denis Seyres A1 Alessandra Cabassi A1 John Lambourne A1 Frances Burden A1 Samantha Farrow A1 Harriet McKinney A1 Joana Batista A1 Carly Kempster A1 Maik Pietzner A1 Oliver Slingsby A1 Thong Huy Cao A1 Paulene Quinn A1 Luca Stefanucci A1 Matthew C Sims A1 Karola Rehnstrom A1 Claire Adams A1 Amy Frary A1 Bekir Erguener A1 Roman Kreuzhuber A1 Gabriele Mocciaro A1 Michael Allison A1 Simona D’Amore A1 Albert Koulman A1 Luigi Grassi A1 Julian L Griffin A1 Leong Loke Ng A1 Adrian Park A1 David B Savage A1 Claudia Langenberg A1 Christoph Bock A1 Kate Downes A1 Michele Vacca A1 Paul DW Kirk A1 Mattia Frontini YR 2020 UL http://biorxiv.org/content/early/2020/03/06/2020.03.06.961805.abstract AB Providing a molecular characterisation of cardiometabolic syndrome (CMS) could improve our understanding of its pathogenesis and pathophysiology, and provide a step toward the development of better treatments. To this end, we performed a deep phenotyping analysis of 185 blood donors, 10 obese, and 10 lipodystrophy patients. We analysed transcriptomes and epigenomes of monocytes, neutrophils, macrophages and platelets. Additionally, plasma metabolites including lipids and biochemistry measurements were quantified.Multi-omics integration of this data allowed us to identify combinations of features related to patient status and to order the donor population according to their molecular similarity to patients. We also performed differential analyses on epigenomic, transcriptomic and plasma proteomic data collected from obese individuals before and six months after bariatric surgery. These analyses revealed a pattern of abnormal activation of immune cells in obese individuals and lipodystrophy patients, which was partially reverted six months after bariatric surgery.