Urinary Proteome Monitoring for Transplant Injury

移植损伤的尿液蛋白质组监测

基本信息

  • 批准号:
    8520707
  • 负责人:
  • 金额:
    $ 39.36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-08-23 至 2014-07-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Our goal in this study is to discovery of diagnostic non-invasive biomarkers in a large cohort (n=580) patient urine samples for different graft injury phenotypes in pediatric kidney transplantation. Kidney transplantation is the treatment of choice for children with end stage kidney disease. Graft survival is limited by the accrual of different injuries such as acute rejection (AR), chronic allograft nephropathy (CAN), and viral infection with the BK virus (BKV), which are indistinguishable by simply monitoring the serum creatinine and require an invasive biopsy for diagnosis of established injury. Urine is an ultrafiltrate of plasma and a direct filtrate of the kidney and provides a valuable resource for monitoring graft health and dysfunction. We propose to employ cutting-edge, comprehensive analysis of the urinary proteome by LC-MALDI based peptidomics and LC-MS/MS based soluble protein analysis of human urine. An environment of outstanding bioinformatics and the availability of a comprehensive Clinical Database will support high-throughput data analysis for selection of 50 most significant peptides and proteins for differentiating different graft injury phenotypes- AR, CAN, BKV and stable functioning grafts (STA). To enable selection of the most biologically relevant candidates, robust integrative proteogenomic data analysis will be performed using overlapping biopsy microarray data and urine proteomic data from the same patient, collected at the same time-point. Specific and sensitive non-invasive urinary biomarkers discovery for different phenotypes of graft injury will undergo pre-clinical validation by MRM on an independent set of 400 urine samples for diagnosis and prediction. The deliverable from this proposal is to enrich for ~10 urinary protein biomarkers that can be used for clinical monitoring of graft injury, replacing the invasive transplant biopsy. PUBLIC HEALTH RELEVANCE: In the absence of an effective noninvasive way of diagnosing acute injury, kidney biopsy is the only way to monitor the clinical progress the transplanted kidney. In this study, we propose a comprehensive search for biomarkers that could be later developed as an injury specific clinical test. We are going to use two most powerful proteomic methods to identify these biomarkers which will be first of its kind in the field of transplantation.
描述(由申请人提供):我们在这项研究中的目标是在大队列(n = 580)患者尿液样本中发现针对儿科肾移植中不同移植物损伤表型的诊断性非侵入性生物标志物。肾移植是终末期肾病儿童的首选治疗方法。移植物存活受到不同损伤的限制,例如急性排斥(AR)、慢性同种异体移植肾病(CAN)和 BK 病毒感染(BKV),仅通过监测血清肌酐无法区分这些损伤,需要进行侵入性活检来诊断已确定的损伤。尿液是血浆的超滤液和肾脏的直接滤液,为监测移植物健康和功能障碍提供了宝贵的资源。我们建议通过基于 LC-MALDI 的肽组学和基于 LC-MS/MS 的人尿可溶性蛋白分析,对尿液蛋白质组进行尖端、全面的分析。出色的生物信息学环境和全面的临床数据库的可用性将支持高通量数据分析,以选择 50 种最重要的肽和蛋白质,以区分不同的移植物损伤表型 - AR、CAN、BKV 和功能稳定的移植物 (STA)。为了能够选择生物学上最相关的候选者,将使用在同一时间点收集的同一患者的重叠活检微阵列数据和尿液蛋白质组数据进行强大的综合蛋白质组数据分析。针对不同移植损伤表型的特异性和敏感的非侵入性尿液生物标志物的发现将通过 MRM 对一组独立的 400 个尿液样本进行临床前验证,以进行诊断和预测。该提案的成果是丰富了约 10 种尿蛋白生物标志物,可用于临床监测移植物损伤,取代侵入性移植活检。 公共卫生相关性: 在缺乏诊断急性损伤的有效无创方法的情况下,肾活检是监测移植肾临床进展的唯一方法。在这项研究中,我们建议对生物标志物进行全面的搜索,这些生物标志物随后可以开发为损伤特异性临床测试。我们将使用两种最强大的蛋白质组学方法来鉴定这些生物标志物,这将是移植领域的首创。

项目成果

期刊论文数量(0)
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David G Camp其他文献

David G Camp的其他文献

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{{ truncateString('David G Camp', 18)}}的其他基金

Proteomic Investigations of Alcoholic Hepatitis
酒精性肝炎的蛋白质组学研究
  • 批准号:
    8428142
  • 财政年份:
    2013
  • 资助金额:
    $ 39.36万
  • 项目类别:
Proteomic Investigations of Alcoholic Hepatitis
酒精性肝炎的蛋白质组学研究
  • 批准号:
    8735047
  • 财政年份:
    2013
  • 资助金额:
    $ 39.36万
  • 项目类别:
Urinary Proteome Monitoring for Transplant Injury
移植损伤的尿液蛋白质组监测
  • 批准号:
    8131911
  • 财政年份:
    2010
  • 资助金额:
    $ 39.36万
  • 项目类别:
Urinary Proteome Monitoring for Transplant Injury
移植损伤的尿液蛋白质组监测
  • 批准号:
    8549203
  • 财政年份:
    2010
  • 资助金额:
    $ 39.36万
  • 项目类别:
Urinary Proteome Monitoring for Transplant Injury
移植损伤的尿液蛋白质组监测
  • 批准号:
    7992872
  • 财政年份:
    2010
  • 资助金额:
    $ 39.36万
  • 项目类别:
Urinary Proteome Monitoring for Transplant Injury
移植损伤的尿液蛋白质组监测
  • 批准号:
    8866586
  • 财政年份:
    2010
  • 资助金额:
    $ 39.36万
  • 项目类别:
Urinary Proteome Monitoring for Transplant Injury
移植损伤的尿液蛋白质组监测
  • 批准号:
    8326684
  • 财政年份:
    2010
  • 资助金额:
    $ 39.36万
  • 项目类别:

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