Supplementary Material for: Proteomics to metabolomics: A new insight into the pathogenesis of hypertensive nephropathy

Abstract
Background: Hypertensive nephropathy (HN) is a high burden disorder and a leading cause of end-stage renal disorder. In spite of huge investigations, the underlying mechanisms are yet largely unknown. Systems biology is a promising approach to provide a comprehensive insight towards this complex disorder.
Methods: Protein expression profiles of kidney tubule and cortex sub-compartments were retrieved from the PRIDE database and the quality of the datasets were assessed using principal component analysis (PCA) and hierarchical clustering. Differentially expressed proteins (DEPs) were detected and their attributed metabolites were enriched and their interactions were assessed in multi-layer networks. Moreover, considering the DEPs and the predicted metabolites, key biomedical phenomena with a leading role in HN pathogenesis were proposed.
Results: Amino acid and purine metabolisms are the most prominent alteration in kidney cortex whereas dysregulation of energy hemostasis is a key pathogenic mechanism in tubule. Besides, actin cytoskeleton disorganization is an enriched pathway in both anatomical areas.
Conclusion: The proteomics profiles of kidney sub-compartments were analyzed using a top-down approach to infer the main pathogenic processes. The constructed holistic map of HN can be exploited to propose novel therapeutic strategies.
Keywords: Hypertensive nephropathy, Proteomics, Metabolomics, Systems biology

摘要
背景：高血压肾病（Hypertensive Nephropathy, HN）是一类负担沉重的疾病，亦是终末期肾病的主要诱因之一。尽管已有大量相关研究，其潜在发病机制仍未完全阐明。系统生物学（Systems Biology）为深入解析这一复杂疾病提供了极具前景的研究思路。
方法：本研究从PRIDE数据库中获取了肾小管与肾皮质亚分区的蛋白质表达谱，并通过主成分分析（Principal Component Analysis, PCA）与层次聚类对数据集质量进行评估。本研究检测了差异表达蛋白质（Differentially Expressed Proteins, DEPs），对其关联代谢物进行富集分析，并通过多层网络解析二者间的相互作用。此外，基于差异表达蛋白质与预测得到的代谢物，本研究提出了在高血压肾病发病机制中发挥核心作用的关键生物医学现象。
结果：研究发现，氨基酸代谢与嘌呤代谢是肾皮质中最显著的代谢紊乱通路，而能量稳态失调则是肾小管病变的关键致病机制。此外，肌动蛋白细胞骨架紊乱在上述两个解剖区域中均为富集度较高的通路。
结论：本研究通过自上而下的分析策略，对肾脏亚分区的蛋白质组学数据进行解析，以推断高血压肾病的主要致病过程。本研究构建的高血压肾病全景图谱可为新型治疗策略的开发提供理论依据。
关键词：高血压肾病，蛋白质组学，代谢组学，系统生物学