S1 Raw data -

Introduction Lupus nephritis (LN) is one of the most frequent and serious organic manifestations of systemic lupus erythematosus (SLE). Autophagy, a new form of programmed cell death, has been implicated in a variety of renal diseases, but the relationship between autophagy and LN remains unelucidated. Methods We analyzed differentially expressed genes (DEGs) in kidney tissues from 14 LN patients and 7 normal controls using the GSE112943 dataset. Key modules and their contained genes were identified utilizing weighted gene co-expression network analysis (WGCNA). Differentially expressed autophagy-related genes (DE-ARGs) among DEGs, key module genes and autophagy-related genes (ARGs) were obtained by venn plot, and subjected to protein-protein interaction network construction. Two machine learning methods were applied to identify signature genes. The area under the receiver operating characteristic (ROC) curves was used to assess the accuracy of the signature genes. We also analyzed immune cell infiltration in LN. Additionally, the association between key genes and kidney diseases was predicted. Finally, key genes expression in kidney was verified by clinical samples and animal experiments. Results A total of 10304 DEGs were identified in GSE1129943 and 29 modules were identified in WGCNA. Among them, the brown module and coral 2 module exhibited significant correlation with LN (cor = 0.86, -0.84, p<0.001). Machine learning techniques identified 5 signature genes, but only 2 were validated in the external dataset GSE32591, namely MAP1LC3B (AUC = 0.920) and TNFSF10 (AUC = 0.937), which are involved in autophagy and apoptosis. Immune infiltration analysis suggested that these key genes may be associated with immune cell infiltration in LN. In addition, these genes have been linked to a variety of renal diseases, and their expression was verified in kidney tissues in LN patients and lupus mice. Conclusion MAP1LC3B and TNFSF10 may be key autophagy-related genes in LN. These key genes have the potential to provide new insights into the molecular diagnosis and treatment of LN.## 引言 狼疮性肾炎（Lupus nephritis, LN）是系统性红斑狼疮（Systemic lupus erythematosus, SLE）最常见且严重的脏器受累表现之一。自噬（Autophagy）作为一种新型程序性细胞死亡形式，已被证实与多种肾脏疾病密切相关，但自噬与狼疮性肾炎之间的关联仍未明确阐明。 ## 方法 本研究利用GSE112943数据集，对14例狼疮性肾炎患者与7例正常对照者的肾脏组织中的差异表达基因（Differentially expressed genes, DEGs）进行分析。采用加权基因共表达网络分析（Weighted gene co-expression network analysis, WGCNA）筛选关键模块及其包含的基因。通过韦恩图获取差异表达基因、关键模块基因与自噬相关基因（Autophagy-related genes, ARGs）三者的交集，即差异表达自噬相关基因（Differentially expressed autophagy-related genes, DE-ARGs），并构建其蛋白质相互作用网络。采用两种机器学习方法筛选特征基因，以受试者工作特征曲线（Receiver operating characteristic, ROC）下面积评估特征基因的诊断效能。本研究同时分析了狼疮性肾炎患者的免疫细胞浸润情况，此外还预测了关键基因与肾脏疾病之间的关联。最后，通过临床样本与动物实验验证了关键基因在肾脏组织中的表达情况。 ## 结果 本研究在GSE1129943数据集中共筛选得到10304个差异表达基因，通过加权基因共表达网络分析得到29个基因模块。其中，棕色模块与珊瑚色2模块与狼疮性肾炎呈显著相关性（相关系数分别为0.86与-0.84，p<0.001）。机器学习方法共筛选得到5个特征基因，但仅MAP1LC3B（曲线下面积AUC=0.920）与TNFSF10（AUC=0.937）在外部数据集GSE32591中得到验证，二者均参与自噬与细胞凋亡过程。免疫浸润分析结果显示，这些关键基因可能与狼疮性肾炎的免疫细胞浸润相关。此外，这些基因已被证实与多种肾脏疾病相关，且在狼疮性肾炎患者及狼疮模型小鼠的肾脏组织中验证了其表达情况。 ## 结论 MAP1LC3B与TNFSF10或为狼疮性肾炎中关键的自噬相关基因，这些关键基因可为狼疮性肾炎的分子诊断与治疗提供新的研究思路。