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Provedor de dados:  Nature Precedings
País:  United Kingdom
Título:  Aptamer-based multiplexed proteomic technology for biomarker discovery
Autores:  Larry Gold
Deborah Ayers
Jennifer Bertino
Christopher Bock
Ashley Bock
Edward N. Brody
Jeff Carter
Virginia Cunningham
Andrew Dalby
Bruce E. 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 R. 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 K. Nelson
Dan Nieuwlandt
Malti Nikrad
Urs Ochsner
Rachel M. 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 D. Vaught
Mike Vrkljan
Jeffrey J. Walker
Mike Watrobka
Sheela Waugh
Allison Weiss
Sheri Wilcox
Alexey Wolfson
Steve Wolk
Chi Zhang
Dom Zichi
Data:  2010-06-14
Ano:  2010
Palavras-chave:  Biotechnology
Molecular Cell Biology
Resumo:  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.
Tipo:  Manuscript
Fonte:  Nature Precedings
Direitos:  Creative Commons Attribution 3.0 License

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