Advances in human proteomics at high scale with the SOMAscan proteomics platform.

In 1997, while still working at NeXstar Pharmaceuticals, several of us made a proteomic bet. We thought then, and continue to think, that proteomics offers a chance to identify disease-specific biomarkers and improve healthcare. However, interrogating proteins turned out to be a much harder problem than interrogating nucleic acids. Consequently, the 'omics' revolution has been fueled largely by genomics. High-scale proteomics promises to transform medicine with personalized diagnostics, prevention, and treatment. We have now reached into the human proteome to quantify more than 1000 proteins in any human matrix - serum, plasma, CSF, BAL, and also tissue extracts - with our new SOMAmer-based proteomics platform. The surprising and pleasant news is that we have made unbiased protein biomarker discovery a routine and fast exercise. The downstream implications of the platform are substantial.

[1]  J. Ninio.  Kinetic amplification of enzyme discrimination. , 1975, Biochimie.

[2]  S. Spiegelman,et al.  SEQUENCE COMPLEMENTARIITY OF T2-DNA AND T2-SPECIFIC RNA* , 2022 .

[3]  Pei Wang,et al.  A targeted proteomics–based pipeline for verification of biomarkers in plasma , 2011, Nature Biotechnology.

[4]  Rachel Ostroff,et al.  The stability of the circulating human proteome to variations in sample collection and handling procedures measured with an aptamer-based proteomics array. , 2010, Journal of proteomics.

[5]  D. Kell,et al.  Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era. , 2004, BioEssays : news and reviews in molecular, cellular and developmental biology.

[6]  Sheri K. Wilcox,et al.  Protein Signature of Lung Cancer Tissues , 2012, PloS one.

[7]  Dan Schneider,et al.  Expanding the chemistry of DNA for in vitro selection. , 2010, Journal of the American Chemical Society.

[8]  Susan E Abbatiello,et al.  Evaluation of Large Scale Quantitative Proteomic Assay Development Using Peptide Affinity-based Mass Spectrometry* , 2011, Molecular & Cellular Proteomics.

[9]  L. Gold,et al.  The use of aptamers in large arrays for molecular diagnostics. , 1999, Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology.

[10]  Christoph H Borchers,et al.  Multi-site assessment of the precision and reproducibility of multiple reaction monitoring–based measurements of proteins in plasma , 2009, Nature Biotechnology.

[11]  Paul Leonard,et al.  Developments in the production of biological and synthetic binders for immunoassay and sensor-based detection of small molecules , 2011 .

[12]  E. Lundberg,et al.  Towards a knowledge-based Human Protein Atlas , 2010, Nature Biotechnology.

[13]  Jerzy Silberring,et al.  Biomarker discovery and clinical proteomics. , 2010, Trends in analytical chemistry : TRAC.

[14]  D. Glass,et al.  A critique of the hypothesis, and a defense of the question, as a framework for experimentation. , 2010, Clinical chemistry.

[15]  Ruedi Aebersold,et al.  Options and considerations when selecting a quantitative proteomics strategy , 2010, Nature Biotechnology.

[16]  Tracy R. Keeney,et al.  Aptamer-based multiplexed proteomic technology for biomarker discovery , 2010, Nature Precedings.

[17]  S. Kingsmore,et al.  Multiplexed protein profiling on microarrays by rolling-circle amplification , 2002, Nature Biotechnology.

[18]  Tracy R. Keeney,et al.  From SOMAmer-Based Biomarker Discovery to Diagnostic and Clinical Applications: A SOMAmer-Based, Streamlined Multiplex Proteomic Assay , 2011, PloS one.

[19]  Larry Gold,et al.  Proteomics and diagnostics: Let's Get Specific, again. , 2008, Current opinion in chemical biology.

[20]  N. Anderson,et al.  The Human Plasma Proteome , 2002, Molecular & Cellular Proteomics.

[21]  E. Petricoin,et al.  Mass Spectrometry-Based Protein Biomarker Discovery and Measurement: Sensitivity is the Greatest Hurdle , 2010, Clinical Proteomics.

[22]  Darryl B. Hardie,et al.  SISCAPA Peptide Enrichment on Magnetic Beads Using an In-line Bead Trap Device*S , 2009, Molecular & Cellular Proteomics.

[23]  Sheri K. Wilcox,et al.  Rapid Histochemistry Using Slow Off-rate Modified Aptamers With Anionic Competition , 2011, Applied immunohistochemistry & molecular morphology : AIMM.

[24]  A. Plückthun,et al.  Engineering novel binding proteins from nonimmunoglobulin domains , 2005, Nature Biotechnology.

[25]  Amanda M White,et al.  Evaluation of surface chemistries for antibody microarrays. , 2007, Analytical biochemistry.

[26]  C. Borrebaeck,et al.  High-throughput proteomics using antibody microarrays: an update , 2007, Expert review of molecular diagnostics.

[27]  Amanda G. Paulovich,et al.  An Automated and Multiplexed Method for High Throughput Peptide Immunoaffinity Enrichment and Multiple Reaction Monitoring Mass Spectrometry-based Quantification of Protein Biomarkers* , 2009, Molecular & Cellular Proteomics.

[28]  P. O’Farrell.  High resolution two-dimensional electrophoresis of proteins. , 1975, The Journal of biological chemistry.

[29]  Hanlee P. Ji,et al.  Multiplexed protein detection by proximity ligation for cancer biomarker validation , 2007, Nature Methods.

[30]  Darryl B. Hardie,et al.  Mass spectrometric quantitation of peptides and proteins using Stable Isotope Standards and Capture by Anti-Peptide Antibodies (SISCAPA). , 2004, Journal of proteome research.

[31]  Ruedi Aebersold,et al.  Mass spectrometry based targeted protein quantification: methods and applications. , 2009, Journal of proteome research.

[32]  Michael E Phelps,et al.  Systems Biology and New Technologies Enable Predictive and Preventative Medicine , 2004, Science.

[33]  M. Mann,et al.  Quantitative, high-resolution proteomics for data-driven systems biology. , 2011, Annual review of biochemistry.

[34]  J. Hopfield.  Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Hanlee P. Ji,et al.  Next-generation DNA sequencing , 2008, Nature Biotechnology.

[36]  B. Chait.  Mass spectrometry in the postgenomic era. , 2011, Annual review of biochemistry.

[37]  Ronald W. Davis,et al.  Quantitative Monitoring of Gene Expression Patterns with a Complementary DNA Microarray , 1995, Science.

[38]  Jonathan D. Vaught,et al.  T7 RNA polymerase transcription with 5-position modified UTP derivatives. , 2004, Journal of the American Chemical Society.

[39]  John R Yates,et al.  Mass spectrometry in high-throughput proteomics: ready for the big time , 2010, Nature Methods.

[40]  Ruedi Aebersold,et al.  A stress test for mass spectrometry–based proteomics , 2009, Nature Methods.

[41]  Robert E. Kearney,et al.  A HUPO test sample study reveals common problems in mass spectrometry-based proteomics , 2009, Nature Methods.

[42]  Arthur D Lander,et al.  The edges of understanding , 2010, BMC Biology.

[43]  M. Uhlén,et al.  Affinity reagents for lab on chips. , 2011, Lab on a chip.

[44]  Gary J. Nabel,et al.  The Coordinates of Truth , 2009, Science.

[45]  L. Gold,et al.  Let's get specific: the relationship between specificity and affinity. , 1995, Chemistry & biology.

[46]  Michel H M Eppink,et al.  Alternative affinity tools: more attractive than antibodies? , 2011, The Biochemical journal.

[47]  J. Lupski,et al.  The complete genome of an individual by massively parallel DNA sequencing , 2008, Nature.

[48]  Stephen A. Williams,et al.  Unlocking Biomarker Discovery: Large Scale Application of Aptamer Proteomic Technology for Early Detection of Lung Cancer , 2010, PloS one.

[49]  Larry Gold,et al.  High-content affinity-based proteomics: unlocking protein biomarker discovery , 2010, Expert review of molecular diagnostics.