The objective of this program project is to integrate three different genomic disciplines to advance our working understanding of clinical kidney transplantation. Patients with acute rejection and chronic allograft nephropathy will be compared to patients without rejection and long term, well-functioning transplants. Specifically, we propose to use both kidney transplant biopsies and peripheral blood lymphocytes. Gene expression profiling will be done using Affymetrix oligonucleotide-based microarrays (Project 1). Proteomics will involve the use of liquid chromatography coupled with linear ion trap mass spectrometry (Project 2). Gene candidates identified by data generated with these two technologies will comprise a set of 500 genes for which we will perform complex trait SNP genetic analysis (Project 3). The Bioinformatics and Statistics Core will provide the bioinformatics and statistical support for all projects. All data will flow to the Core for both advanced analysis and archiving. At the first level this support will include monitoring experimental designs for statistical integrity, organizing complex data sets generated in each Project so that they are more accessible to the Principal Investigators for interpretation and discovery and perform data mining using bioinformatic tools. Clinical data entered into the web site at Scripps will also be integrated with these efforts in a real-time fashion. At the second level the Core will supervise the selection and statistical validation of the 500 gene candidate set based on gene expression and proteomic data intended for complex trait genetics in Project 3. We will use supervised and unsupervised data mining methods such as clustering and class prediction tools. We will also identify differentially expressed genes and proteins in the different kidney transplant group comparisons. At the third level the Core will integrate data generated in all three Projects so that connections, pathways and mechanisms can be recognized, defined and validated including possibly novel relationships between patient and donor genetics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI063603-03
Application #
7280811
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
3
Fiscal Year
2006
Total Cost
$304,427
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Meng, Xiangzhi; Riley, Nicole; Thompson, Ryan et al. (2018) Investigate Global Chromosomal Interaction by Hi-C in Human Naive CD4 T Cells. Methods Mol Biol 1712:239-252
Gioia, Louis; Siddique, Azeem; Head, Steven R et al. (2018) A genome-wide survey of mutations in the Jurkat cell line. BMC Genomics 19:334
Kurian, S M; Velazquez, E; Thompson, R et al. (2017) Orthogonal Comparison of Molecular Signatures of Kidney Transplants With Subclinical and Clinical Acute Rejection: Equivalent Performance Is Agnostic to Both Technology and Platform. Am J Transplant 17:2103-2116
Buzby, Jeffrey S; Williams, Shirley A; Schaffer, Lana et al. (2017) Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li-Fraumeni syndrome. Cancer Genet 211:9-17
Modena, Brian D; Bleecker, Eugene R; Busse, William W et al. (2017) Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease. Am J Respir Crit Care Med 195:1449-1463
Modena, B D; Milam, R; Harrison, F et al. (2017) Changes in Urinary Microbiome Populations Correlate in Kidney Transplants With Interstitial Fibrosis and Tubular Atrophy Documented in Early Surveillance Biopsies. Am J Transplant 17:712-723
LaMere, Sarah A; Thompson, Ryan C; Meng, Xiangzhi et al. (2017) H3K27 Methylation Dynamics during CD4 T Cell Activation: Regulation of JAK/STAT and IL12RB2 Expression by JMJD3. J Immunol 199:3158-3175
LaMere, S A; Thompson, R C; Komori, H K et al. (2016) Promoter H3K4 methylation dynamically reinforces activation-induced pathways in human CD4 T cells. Genes Immun 17:283-97
Leventhal, J R; Mathew, J M; Salomon, D R et al. (2016) Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers. Am J Transplant 16:221-34
Modena, B D; Kurian, S M; Gaber, L W et al. (2016) Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes. Am J Transplant 16:1982-98

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