Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Search for singly and pair-produced leptoquarks coupling to third-generation fermions in proton-proton collisions at root s=13 TeV

A search for leptoquarks produced singly and in pairs in proton-proton collisions is presented. We consider the leptoquark (LQ) to be a scalar particle of charge -1/3e coupling to a top quark plus a tau lepton (t tau) or a bottom quark plus a neutrino (b nu), or a vector particle of charge +2/3e, coupling to t nu or b tau. These choices are motivated by models that can explain a series of anomalies observed in the measurement of B meson decays. In this analysis the signatures t tau nu b and t tau nu are probed, using data recorded by the CMS experiment at the CERN LHC at root s = 13 TeV and that correspond to an integrated luminosity of 137 fb(-1). These signatures have not been previously explored in a dedicated search. The data are found to be in agreement with the standard model prediction. Lower limits at 95% confidence level are set on the LQ mass in the range 0.98-1.73 TeV, depending on the LQ spin and its coupling lambda to a lepton and a quark, and assuming equal couplings for the two LQ decay modes considered. These are the most stringent constraints to date on the existence of leptoquarks in this scenario. (C) 2021 The Author(s). Published by Elsevier B.V.Peer reviewe