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首页> 外文期刊>The Journal of molecular diagnostics: JMD >Probabilistic (Bayesian) modeling of gene expression in transplant glomerulopathy.
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Probabilistic (Bayesian) modeling of gene expression in transplant glomerulopathy.

机译：移植肾小球病中基因表达的概率（贝叶斯）建模。

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Transplant glomerulopathy (TG) is associated with rapid decline in glomerular filtration rate and poor outcome. We used low-density arrays with a novel probabilistic analysis to characterize relationships between gene transcripts and the development of TG in allograft recipients. Retrospective review identified TG in 10.8% of 963 core biopsies from 166 patients; patients with stable function were studied for comparison. The biopsies were analyzed for expression of 87 genes related to immune function and fibrosis by using real-time PCR, and a Bayesian model was generated and validated to predict histopathology based on gene expression. A total of 57 individual genes were increased in TG compared with stable function biopsies (P < 0.05). The Bayesian analysis identified critical relationships between ICAM-1, IL-10, CCL3, CD86, VCAM-1, MMP-9, MMP-7, and LAMC2 and allograft pathology. Moreover, Bayesian models predicted TG when derived from either immune function (area under the curve [95% confidence interval] of 0.875 [0.675 to 0.999], P = 0.004) or fibrosis (area under the curve [95% confidence interval] of 0.859 [0.754 to 0.963], P < 0.001) gene networks. Critical pathways in the Bayesian models were also analyzed by using the Fisher exact test and had P values <0.005. This study demonstrates that evaluating quantitative gene expression profiles with Bayesian modeling can identify significant transcriptional associations that have the potential to support the diagnostic capability of allograft histology. This integrated approach has broad implications in the field of transplant diagnostics.
机译：移植肾小球病变（TG）与肾小球滤过率的快速下降和不良的预后有关。我们使用具有新的概率分析的低密度阵列来表征同种异体移植受体中基因转录本与TG发育之间的关系。回顾性研究在166例患者的963例活检组织中，TG占10.8％;对功能稳定的患者进行研究以进行比较。通过使用实时PCR分析活检组织中与免疫功能和纤维化相关的87个基因的表达，并生成贝叶斯模型并进行验证以基于基因表达预测组织病理学。与稳定的功能活检相比，TG中共有57个个体基因增加（P <0.05）。贝叶斯分析确定了ICAM-1，IL-10，CCL3，CD86，VCAM-1，MMP-9，MMP-7和LAMC2与同种异体移植病理之间的关键关系。此外，贝叶斯模型预测TG源自免疫功能（0.875 [0.675至0.999]曲线下区域[95％置信区间]，P = 0.004）或纤维化（0.859 [95％置信区间]曲线下面积）。 [0.754至0.963]，P <0.001）基因网络。贝叶斯模型中的关键路径也使用Fisher精确检验进行了分析，其P值<0.005。这项研究表明，用贝叶斯模型评估定量基因表达谱可以鉴定出重要的转录关联，这些关联具有支持同种异体移植组织学诊断能力的潜力。这种集成方法在移植诊断领域具有广泛的意义。

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