Abstract
A key concept in medical science is that by comparing DNA, RNA, or proteins from healthy and diseased individuals, insight can be gained into the etiology of disease leading to better diagnostics and therapeutics. In this context, biorepositories have long played a key role by allowing the accumulation of biological fluids and tissues from large numbers of individuals for longitudinal or cross-sectional comparisons. Approaches to understanding human disease are based on the central dogma that information flow in living systems is from DNA to RNA to protein. At all levels, aberrations could indicate either the presence of disease or suggest underlying mechanisms of disease. However, historically DNA and RNA have been more useful for identifying risk of disease than the presence of disease, except in surgical specimens. Proteins in biological fluids [blood, urine, aspirates, etc.] have played a more prominent role in diagnostics. Indeed given that proteins are in essence the effectors of gene expression a long held goal has been to associate specific proteins in peripheral circulation that indicate the presence of disease, e.g. biomarkers of disease, especially early disease before the appearance of symptoms or other clinical indicators.
This presentation will focus on issues associated with the use of biorepository fluids in this context. Three issues are fundamental: 1) specimen volume is limited and precious, 2) specimen processing requirements are not known a'priori, and 3) analytical targets are often not precisely defined. Limited specimen volume is an inherent problem because each blood draw represents a discrete end point. Unlike nucleic acids, proteins are subject to numerous post-translational biological modifications and to extensive, often rapid, degradation post specimen collection. These issues drive method development and validation, ultimately determining the amount and quality of data that can be obtained from biorepository specimens. Protein analytical methods will be reviewed from this perspective with emphasis on recent developments in multi-analyte systems and newer, highly sensitive methods.
Citation Format: Patrick M. Sluss. New assays, old specimens: Multiplexing for plasma and urine. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr IA01.