a functional proteomic method for biomarker discovery功能蛋白质组学方法,生物标志物的发现.pdfVIP

A Functional Proteomic Method for Biomarker Discovery 1,2 1 1 1 1 Fred Reynolds , Nivedha Panneer , Christopher M. Tutino , Michael Wu , William R. Skrabal , Christopher Moskaluk3,4, Kimberly A. Kelly1,2* 1 Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America, 2 Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia, United States of America, 3 Department of Pathology, University of Virginia, Charlottesville, Virginia, United States of America, 4 Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, United States of America Abstract The sequencing of the human genome holds out the hope for personalized medicine, but it is clear that analysis of DNA or RNA content alone is not sufficient to understand most disease processes. Proteomic strategies that allow unbiased identification of proteins and their post-transcriptional and -translation modifications are an essential complement to genomic strategies. However, the enormity of the proteome and limitations in proteomic methods make it difficult to determine the targets that are particularly relevant to human disease. Methods are therefore needed that allow rational identification of targets based on function and relevance to disease. Screening methodologies such as phage display, SELEX, and small-molecule combinatorial chemistry have been widely used to discover specific ligands for cells or tissues of interest, such as tumors. Those ligands can be used in turn as affinity probes to identify their cognate molecular targets when they are not known in advance. Here we report an easy, robust and generally