Aptamer-based multiplexed proteomic technology for biomarker discovery

• DOI: 10.1038/npre.2010.4538.1
• Publication Date: 2019-07-18T10:02:39Z
• Authors: Larry Gold; Deborah Ayers; Jennifer Bertino; Christopher Bock; Ashley Bock; Edward Brody; Jeff Carter; Virginia Cunningham; Andrew Dalby; Bruce Eaton; Tim Fitzwater; Dylan Flather; Ashley Forbes; Trudi Foreman; Cate Fowler; Bharat Gawande; Meredith Goss; Magda Gunn; Shashi Gupta; Dennis Halladay; Jim Heil; Joe Heilig; Brian Hicke; Gregory Husar; Nebojsa Janjic; Thale Jarvis; Susan Jennings; Evaldas Katilius; Tracy Keeney; Nancy Kim; Terese Kaske; Tad Koch; Stephan Kraemer; Luke Kroiss; Ngan Le; Daniel Levine; Wes Lindsey; Bridget Lollo; Wes Mayfield; Mike Mehan; Robert Mehler; Michele Nelson; Sally Nelson; Dan Nieuwlandt; Malti Nikrad; Urs Ochsner; Rachel Ostroff; Matt Otis; Thomas Parker; Steve Pietrasiewicz; Dan Resnicow; John Rohloff; Glenn Sanders; Sarah Sattin; Dan Schneider; Britta Singer; Martin Stanton; Alana Sterkel; Alex Stewart; Suzanne Stratford; Jonathan Vaught; Mike Vrkljan; Jeffrey Walker; Mike Watrobka; Sheela Waugh; Allison Weiss; Sheri Wilcox; Alexey Wolfson; Steve Wolk; Chi Zhang; Dom Zichi
• Keywords: Aptamer; Biomarker Discovery; Proteome

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