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Aptamer-based proteomic profiling reveals novel candidate biomarkers of cardiovascular disease

ABSTRACT: Ngo D, Sinha S, Shen D, Kuhn E, Keyes M, Shi X, Benson M, O'Sullivan J, Keshishian H, Farrell L, Fifer MA, Vasan RS, Sabatine M, Larson MG, Carr SA, Wang TJ, Gerszten RE. Circulation 2016. Emerging proteomic technologies are beginning to permit the systematic characterization of human plasma samples. DNA-aptamer based technologies may address limitations of existing proteomic techniques, including low sample throughput, which have prevented proteomic analyses of large cohorts. We applied an aptamer-based proteomic technology that measures 1,129 proteins to identify potential novel biomarkers of cardiovascular disease. We found very early markers of myocardial injury in a robust, clinically-relevant perturbational model of planned myocardial injury, patients undergoing septal ablation for hypertrophic cardiomyopathy. We then tested whether the platform could detect novel associations between proteins and cardiovascular risk factors in individuals without overt cardiovascular disease using archived samples from the Framingham Heart Study. Further, we developed a new workflow integrating DNA-based immunoaffinity with mass spectrometry to analytically validate the specificity of aptamer findings. Our results highlight an emerging proteomics tool capable of profiling over one thousand low abundance analytes with high sensitivity and high precision, applicable both to well-phenotyped perturbational studies as well as large human cohorts.

INSTRUMENT(S): TSQ Quantiva, Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000079908 | MassIVE | Thu Jul 14 09:01:00 BST 2016

REPOSITORIES: MassIVE

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Aptamer-based proteomic profiling reveals novel candidate biomarkers of cardiovascular disease

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