Genomics for Kidney Transplantation

项目描述（由申请人提供）：本项目的主题是测试基因表达谱（项目1）、蛋白质组学（项目2）和复杂性状遗传学（项目3）的发展技术的应用，以提高我们对肾移植临床问题和移植基础生物学的理解。我们的观点是，这是一种肾移植的系统生物学方法。这些努力得到了一组具有所有三个科学领域专业知识以及临床肾移植和生物信息学和统计学专业知识的合作者的支持。

DESCRIPTION (provided by applicant): The theme of this Program Project is to test the application of developing technologies for gene expression profiling (Project 1), proteomics (Project 2) and complex trait genetics (Project 3) to advance our understanding of kidney transplantation in the context of both its clinical problems and the basic biology of transplantation. Our view is that this is a systems biology approach to kidney transplantation. These efforts are supported by a group of collaborators with expertise in all three scientific areas as well as expertise in clinical kidney transplantation and bioinformatics and statistics. The kind of data we will generate will be of two kinds: diagnostic and discovery. The diagnostic component will consist of potentially complex gene and protein expression signatures that will have statistically valid correlations to specific clinical events like acute rejection, chronic allograft nephropathy and long term well-functioning transplants with no rejection. The discovery component will consist of identifying within these complex genomic signatures, specific gene candidates that correlate with transplant events and outcomes. Our hypotheses are: 1) that gene and protein expression signatures can be identified in PBL and kidney transplant biopsies that correlate with biopsy-proven acute rejection and chronic allograft nephropathy, 2) that gene and protein expression profiles provide insights into the molecular pathways involved in both the host immune response and the donor organ's response to transplantation, and 3) that the adequacy of immunosuppression, as defined by the absence of rejection-related gene and protein expression, can be determined by the gene and protein expression profiles. We also propose to examine the possibility that race and sex will influence at least a subset of gene transcripts and proteins expressed post transplant and correlate with outcomes. The first objective of this application will be to integrate data on gene expression profiling in parallel with data generated by proteomics (Project 2) and complex trait genetics (Project 3) to advance a more comprehensive understanding of the molecular basis of clinical kidney transplantation. The second is to establish the requisite proof of principle to design a prospective clinical trial to test the hypothesis that PBL profiles can be used to monitor the efficacy of immunosuppression in 'real-time'.