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Genetic Engineering & Biotechnology News | GENengnews.com | JULY 2016 | 23 neous measurements that perform like indi- vidual ELISAs. 1,3 To perform the assay, SOMAmer reagents are immobilized to a streptavidin-bead using a biotin on the reagent. The bead-bound reagents are then mixed with biological samples allowing proteins to bind during catch-1, Figure 2A,B. Unbound proteins are washed away before bound proteins are tagged with biotin, Figure 2C. A photocleavable linker then allows light-activated release of the complexes into a buffer formulated to reduce nonspecifc complexes, Figure 2D. Since all SOMAmer reagents are oligonucleotides, they are in- herently negatively charged. A polyanionic competitor facilitates the "kinetic specifc- ity enrichment" that reduces weakly bound, nonspecifc complexes, Figure 2E. The biotin on the protein is then used to immobilize high-affnity complexes that re- main after kinetic challenge in catch-2, Fig- ure 2F, and unbound SOMAmer reagents are washed away. At this point beads retain com- plexes of proteins and SOMAmer reagents. In the fnal steps of the assay, SOMAmer re- agents are dissociated from these complexes, Figure 2G, hybridized to complementary sequences on a microarray, Figure 2H, and quantifed by fuorescence. The fuorescence signal for each SO- MAmer reagent is directly proportional to the amount of protein in the initial sample. This transformation from protein to nucleic acid signal is made possible by a special fea- ture of nucleic acid ligands: the same unique sequence determines both folding into a 3D structure with precise shape complementar- ity to its target, as well as hybridization to complementary probes. Large-Scale Protein Profling The advent of large-scale proteomic pro- fling opens a world of applications in bio- medical science just as large-scale genomic profling did. Utilities range from elucidating fundamental biology questions like disease natural history to biomarker discovery for diagnostics, drug development, discovering new drug targets, and elucidating mecha- nisms of action. A powerful example of large-scale pro- teomic profling is a study of Duchenne Mus- cular Dystrophy (DMD) comparing blood profles from DMD and control subjects to fnd new therapeutic targets in this disease. 4 Results comparing ~4,000 proteins between DMD and control subjects (Figure 3) revealed a wealth of differential expression. In another notable example, large-scale proteomic profling discovered a circulat- ing protein, GDF11/8, in young mice that reduced cardiac hypertrophy in old mice. 5 This discovery sparked a wave of interest and research to understand complex biology with broad implications in musculo-skeletal disease. A fnal example is a recent study (in press) of cardiovascular disease that ranks among the largest proteomic profling studies ever conducted. Blood from 2,700 case and con- trol samples were profled, collecting more than three million measurements in a matter of weeks. The results were used to develop a promising biomarker test to manage patients with previous cardiovascular events based on risk of suffering another event. Given that the bulk of biological func- tion is manifested by changes in proteins, proteomics holds great potential to impact numerous applications. This potential has yet to be fully realized largely due to limi- tations in existing proteomics technologies, particularly the need to choose between a technique that measures many proteins in a few samples and one that measures a few proteins in many samples. The SOMAscan assay addresses these limitations by allowing rapid profling of thousands of proteins in thousands of samples, providing a powerful tool for better understanding of biological processes with broad utility in biomedical re- search. www.moleculardevices.com | 800.635.5577 For Research Use Only. Not for use in diagnostic procedures. © 2016 Molecular Devices, LLC. All Rights Reserved. The trademarks mentioned herein are the property of Molecular Devices, LLC or their respective owners. Unleash your brilliance™ ZOOM Y X Position your research with our new ImageXpress® Micro 4 High-Content Imaging System • Tackle your toughest assays with an imaging platform that adapts to your needs • Image over 15 million cells per hour in a 3-color cell scoring assay • Acquire and analyze in both 2D and 3D using our seamless, integrated end-to-end solution • Drive your research with a system that builds on over 30 years of innovation in imaging moleculardevices.com/ixm4 OMICS Assay Tutorial Dominic Zichi (dzichi@somalogic.com) is director of bioinformatics, Sheri Wilcox is senior director, discovery sciences, Jeffrey Walker is director, strategic alliances and technology, and Nebojsa Janjic is CSO at SomaLogic. Website: www.somalogic.com. References available online at www.genengnews.com.