Nephrology - Transplantation Department, UMR_S. INSERM UMR_S 1109, ImmunoRhumatologie Moléculaire, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Institut d'Immunologie et d'Hématologie, 67085, Strasbourg, France.
Laboratoire de Spectrométrie de Masse BioOrganique, University of Strasbourg, Centre National de la Recherche Scientifique, Institut Pluridisciplinaire Hubert Curien, UMR 7178, 67037, Strasbourg, France.
Proteomics Clin Appl. 2019 Mar;13(2):e1800091. doi: 10.1002/prca.201800091. Epub 2019 Feb 4.
There is a need for accurate, robust, non-invasive methods to provide early diagnosis of graft lesions after kidney transplantation. A multitude of proteomic biomarkers for the major kidney allograft disease phenotypes defined by the BANFF classification criteria have been described in literature. None of these biomarkers have been established in the clinic. A key reason for this is the lack of clinical validation which is difficult, as even the gold standard of diagnosis, kidney biopsy, is often ambiguous. The semantic clustering by ReviGO on top of transcriptomic pathway analysis is evaluated to connect histological and transcriptomic kidney allograft disease characteristics with proteomic biomarker qualification. By using public data generated in microarray studies of kidney allograft tissue, biological processes and key molecules specifically associated with the different kidney allograft disease phenotypes are identified. Semantic clustering holds the promise to guide adaptation of proteomic marker panels to molecular pathology. This can support the development of noninvasive tests (e.g. in urine, by capillary electrophoresis mass spectrometry) that simultaneously detect diverse kidney allograft phenotypes with high accuracy and sensitivity.
需要准确、稳健、非侵入性的方法来提供肾移植后移植物病变的早期诊断。文献中已经描述了大量用于定义 BANFF 分类标准的主要肾移植疾病表型的蛋白质组生物标志物。这些生物标志物都没有在临床上确立。造成这种情况的一个关键原因是缺乏临床验证，这是很困难的，因为即使是诊断的金标准——肾活检，也常常是不明确的。通过 ReviGO 对转录组途径分析进行语义聚类，评估其将组织学和转录组肾移植疾病特征与蛋白质组生物标志物定性联系起来的能力。通过使用微阵列研究肾移植组织生成的公共数据，确定了与不同肾移植疾病表型特异性相关的生物过程和关键分子。语义聚类有望指导蛋白质标志物面板适应分子病理学。这可以支持开发非侵入性测试（例如通过毛细管电泳质谱法在尿液中），以高精度和高灵敏度同时检测多种肾移植表型。
