慢性病的特征和分类,通过空间MIST和深度学习算法
Arafat Meah1, Nehaben A Gujarati2, Vivette D D'Agati3
1Multiplex Biotechnology Laboratory, Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, United States.
American journal of physiology. Renal physiology
|October 24, 2025
概括
空间MIST分析揭示了与慢性病 (CKD) 纤维化进展相关的关键蛋白质标记物和空间模式. 这种方法有助于对疾病的严重程度进行分类,并发现CKD的新生物标志物.
科学领域:
- 腎病理學和病理學.
- 蛋白质组学和空间生物学
- 计算生物学和生物信息学
背景情况:
- 慢性病 (CKD) 涉及纤维化,这是一个影响细胞和分子结构的复杂过程.
- 了解蛋白质的空间组织对于解决CKD中纤维性重塑至关重要.
- 现有的方法可能无法完全捕捉纤维化病的高维空间复杂性.
研究的目的:
- 应用信号标记的空间复杂免疫染色 (Spatial MIST) 用于人类脏活检的高维蛋白质组分析.
- 为了研究纤维脏组织中的结构变化,细胞类型分布和空间关系.
- 识别与CKD进展和纤维化严重程度相关的空间特征和蛋白质标记.
主要方法:
- 利用空间MIST,一种蛋白质基因平台,对不同级别纤维化的人类脏活检.
- 量化了22种蛋白质标记物,通过单细胞分辨率在全球和间歇性体中.
- 采用空间近距离分析,统一的多元近似和投影 (UMAP) 聚类,以及与功能指标的相关性分析.
- 开发了一个图形神经网络 (GNN) 分类器,训练了空间蛋白质组特征.
主要成果:
- 空间近距离分析显示,内皮细胞和上皮细胞标记物的纤维化相关重组.
- 鉴定出 podocyte 和免疫标记物的改变集群,CD31 和β-catenin之间的分离增加.
- 维门丁和α光滑肌肉动蛋白 (α-SMA) 与纤维化严重程度正相关;威尔姆斯瘤1 (WT1) 与功能下降相反相关.
- 一个GNN模型确定了巨素,WT1和维丁作为纤维化等级的关键预测因素.
结论:
- 空间MIST有效地捕捉了CKD进展的分子异质性和空间特征.
- 综合性方法为生物标志物发现和病理的空间信息分类提供了基础.
- 这项研究强调了使用空间蛋白质组数据开发临床可操作的CKD诊断和预后工具的潜力.
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