2021;22(1):19\37. summarize relevant new data on this topic, presented during the 2021 ISTH Congress. 2016 22 This report describes the first large\scale affinity proteomics study in the venous thrombosis field. A total of 408 proteins are targeted in a discovery case/control study (VEBIOS, 2021 24 This report describes the application of machine learning techniques to analyze affinity proteomics data. A total of 444 proteins are targeted in a discovery cohort (Genotyping and Molecular Phenotyping of Venous ThomboEmbolism, 2021 37 This report describes a novel endothelial cell centric affinity proteomics strategy targeting 216 proteins with endothelial enriched expression in a population\based cohort (SCAPIS 2021 36 This publication provides a comprehensive overview of technological developments and applications of mass spectrometry\ and affinity\based plasma proteomics methods, summarizing recent advances and challenges for translating plasma proteomics into clinical utility for precision medicine. It presents the Human Plasma PeptideAtlas build 2021\07 and the Human Extracellular Vesicle PeptideAtlas 2021\06. Open in a Volitinib (Savolitinib, AZD-6094) separate window We used multiplex antibody SBAs targeting 408?selected candidate proteins 22 to perform a proteomics Rabbit Polyclonal to GPRC5B discovery screen in 88 Volitinib (Savolitinib, AZD-6094) cases and 85?matched controls in the Venous Embolism BIOmarker study, where patients were sampled after discontinuation of anticoagulant treatment for a first\time VTE. With access to the large resource of antibody reagents generated as result of the Human Protein Atlas covering 85% of the proteins encoded in the human genome 94 (www.proteinatlas.org), we custom designed suspension bead arrays using 755 antibodies, targeting 408 candidate proteins that were selected for (1) their known roles in the coagulation/fibrinolysis cascade and/or intermediate traits of relevance to thrombosis, (2) their specific expression in endothelial cells (a key cell type involved in thrombosis physiopathology), or (3) encoded by genes identified in pangenomic studies as associated with several cardiovascular disease\linked biological pathways (e.g., platelet function, renal function, inflammation). Following a replication in 580 cases and 589 controls from the French FARIVE study, 22 platelet\derived growth factor (PDGFB) was identified as a novel VTE\associated biomarker, together with von Willebrand factor. To verify the target specificity of the PDGFB capture antibody, we used IC\MS and an ELISA assay. 22 In another study, Razzaq et al. identified Plexin\A4 (PLXNA4) as a new susceptibility gene for PE using an original integrated proteomics and genetics strategy, based on a proteomics analysis of samples from 1388?VTE patients from the MARTHA study, generated with a custom designed SBA of 376 protein\specific antibodies targeting 234 plasma proteins, 23 selected using similar criteria to that described previously. 22 Using the PEA technology, Ten Cate et al. profiled 444 proteins with five 96\plex Olink immunoassay panels (Cardiovascular II and III, Cardiometabolic, Inflammation, Immune Response) in 532 individuals with VTE, sampled at diagnosis, in the Genotyping and Molecular Phenotyping of Venous ThomboEmbolism (GMP\VTE) study. 24 They identified five proteins as more specifically associated with an isolated PE phenotype compared with DVT or DVT\associated PE, Volitinib (Savolitinib, AZD-6094) of which three (interferon\), glial cell\line derived neurotrophic factor, and interleukin\15R were replicated in Olink data from 5778 individuals in the Gutenberg Health Study. Target specificity for the corresponding Olink assays was validated using cis pQTL analysis. In a subsequent study, using the same Olink panels to analyze VTE patients sampled at diagnosis and at 12?months after the index event in GMP\VTE, they identified a body mass\associated proteomic signature of 11 proteins that were consistently related to body mass index in plasma of VTE patients sampled at diagnosis and at 12?months after the index event. 25 However, this signature did not explain the obesity paradox in VTE patients,.