Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada.
Front Immunol. 2024 Sep 27;15:1469500. doi: 10.3389/fimmu.2024.1469500. eCollection 2024.
Kidney transplantation is the optimal treatment for end-stage kidney disease; however, premature allograft loss remains a serious issue. While many high-throughput omics studies have analyzed patient allograft biospecimens, integration of these datasets is challenging, which represents a considerable barrier to advancing our understanding of the mechanisms of allograft loss.
To facilitate integration, we have created a curated database containing all open-access high-throughput datasets from human kidney transplant studies, termed NephroDIP (Nephrology Data Integration Portal). PubMed was searched for high-throughput transcriptomic, proteomic, single nucleotide variant, metabolomic, and epigenomic studies in kidney transplantation, which yielded 9,964 studies.
From these, 134 studies with available data detailing 260 comparisons and 83,262 molecules were included in NephroDIP v1.0. To illustrate the capabilities of NephroDIP, we have used the database to identify common gene, protein, and microRNA networks that are disrupted in patients with chronic antibody-mediated rejection, the most important cause of late allograft loss. We have also explored the role of an immunomodulatory protein galectin-1 (LGALS1), along with its interactors and transcriptional regulators, in kidney allograft injury. We highlight the pathways enriched among LGALS1 interactors and transcriptional regulators in kidney fibrosis and during immunosuppression.
NephroDIP is an open access data portal that facilitates data visualization and will help provide new insights into existing kidney transplant data through integration of distinct studies and modules (https://ophid.utoronto.ca/NephroDIP).
肾移植是治疗终末期肾病的最佳方法;然而,移植物早期失功仍是一个严重的问题。尽管许多高通量组学研究分析了患者移植物生物标本,但这些数据集的整合具有挑战性,这是推进我们对移植物失功机制的理解的一个相当大的障碍。
为了便于整合,我们创建了一个经过精心整理的数据库,其中包含来自人类肾移植研究的所有开放获取高通量数据集,称为 NephroDIP(肾脏病学数据集成门户)。在 PubMed 中搜索高通量转录组学、蛋白质组学、单核苷酸变异、代谢组学和表观基因组学研究,这些研究产生了 9964 项研究。
从中,有 134 项具有可用数据的研究详细描述了 260 个比较和 83262 个分子,被纳入 NephroDIP v1.0。为了说明 NephroDIP 的功能,我们使用该数据库来确定在慢性抗体介导的排斥反应患者中被破坏的常见基因、蛋白质和 microRNA 网络,这是晚期移植物失功的最重要原因。我们还探讨了免疫调节蛋白半乳糖凝集素-1(LGALS1)及其相互作用蛋白和转录调节因子在肾移植损伤中的作用。我们强调了 LGALS1 相互作用蛋白和转录调节因子在肾纤维化和免疫抑制期间富集的途径。
NephroDIP 是一个开放访问的数据门户,它促进了数据可视化,并通过整合不同的研究和模块,将有助于为现有的肾移植数据提供新的见解(https://ophid.utoronto.ca/NephroDIP)。