Discovery of novel biomarkers of thrombosis by plasma proteomics

There is an urgent need for better prediction tools to identify individuals at high risk of first venous thromboembolism (VTE) or VTE recurrence. “Blood would be the ‘ideal’, minimally invasive biomarker source,” explained Professor Jacob Odeberg (Karolinska Universitet Hospital, Stockholm, Sweden). His group uses high throughput separation-, mass-, and affinity-based proteomic approaches to study the protein composition of blood plasma of patients with cardiovascular and thromboembolic disorders, with the aim to develop tests that allow identification of patients with sub-clinical disease.

Classical proteomics targets high abundant protein, but for detection of low abundant proteins dual antibody assays are required. The Swedish Science for Life Laboratory (SciLifeLab) is a national infrastructure for broad spectrum ‘omics’ technology platforms with more than 200 associated research groups. The aim of the Human Protein Atlas is a comprehensive proteome and transcriptome map of all human tissues, using ca. 26.000 antibodies generated in-house.1 The affinity protein platform uses antibodies coupled to color-coded fluorescent beads.

“Blood plasma is extremely complex and, in general, the efficacy of antibodies is strongly context-dependent. This necessitates careful target evaluation early in the process. We were specifically interested in the role of endothelial cell function in cardiovascular and thromboembolic disorders, and in collaboration with dr. Lynn Butler in our institute we recently characterized the ‘endothelial specific transcriptome’, which allowed us to identify novel endothelial cell-enriched genes.”2 The VEREMA affinity proteomics study identified platelet derived growth factor-receptor as a new candidate plasma biomarker for VTE.3

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  1. Uhlén M, et al. Science 2015;347:394
  2. Butler LM, et al. Cell Systems 2016;3:287-301
  3. Bruzelius M, et al. Blood 2016;128:e59-66