通过联合维度缩减与聚类方法识别系统性自身免疫疾病的异质亚组
Identifying heterogeneous subgroups of systemic autoimmune diseases by applying a joint dimension reduction and clustering approach to immunomarkers
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影响因子:6.1
分区:生物学3区 / 数学与计算生物学3区
发表日期:2024 Sep 16
作者:
Chia-Wei Chang, Hsin-Yao Wang, Wan-Ying Lin, Yu-Chiang Wang, Wei-Lin Lo, Ting-Wei Lin, Jia-Ruei Yu, Yi-Ju Tseng
DOI:
10.1186/s13040-024-00389-7
摘要
系统性自身免疫疾病（SADs）的高复杂性阻碍了精准治疗的发展。本研究旨在探讨SADs的异质性。我们采用联合聚类分析方法，将多重对应分析与k-means结合，基于免疫标志物对患者的异质性进行分组，并通过比较免疫标志物和临床表现的差异评估聚类的差异性。研究对象为2001年至2016年在台湾医院接受抗核抗体检测并诊断为SADs（系统性红斑狼疮（SLE）、类风湿关节炎（RA）和干燥综合征（SS））的患者电子健康记录。结果显示，不同的免疫标志物模式将12,000多名患者分为六个不同的亚组。没有任何一个亚组完全由单一SAD组成，这些亚组在临床表现上存在显著差异。SLE和SS患者在六个亚组中的分布更为分散。在SLE患者中，肾功能受损在第3和第6亚组中发生率较高（52%和51%），显著高于其他亚组（p<0.001）。第3亚组中，盘状红斑狼疮的比例也较高（60%），而第6亚组为39%（p<0.001）。SS患者在第3亚组中表现出免疫紊乱发生率最高（63%）以及其他和未具体说明的良性肿瘤（58%），与其他亚组相比具有统计学意义（所有p<0.05）。基于免疫标志物的聚类方法能识别出更多具有临床相关性的SADs亚组，为更精确的诊断提供基础。
Abstract
The high complexity of systemic autoimmune diseases (SADs) has hindered precise management. This study aims to investigate heterogeneity in SADs.We applied a joint cluster analysis, which jointed multiple correspondence analysis and k-means, to immunomarkers and measured the heterogeneity of clusters by examining differences in immunomarkers and clinical manifestations. The electronic health records of patients who received an antinuclear antibody test and were diagnosed with SADs, namely systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), were retrieved between 2001 and 2016 from hospitals in Taiwan.With distinctive patterns of immunomarkers, a total of 11,923 patients with the three SADs were grouped into six clusters. None of the clusters was composed only of a single SAD, and these clusters demonstrated considerable differences in clinical manifestation. Both patients with SLE and SS had a more dispersed distribution in the six clusters. Among patients with SLE, the occurrence of renal compromise was higher in Clusters 3 and 6 (52% and 51%) than in the other clusters (p < 0.001). Cluster 3 also had a high proportion of patients with discoid lupus (60%) than did Cluster 6 (39%; p < 0.001). Patients with SS in Cluster 3 were the most distinctive because of the high occurrence of immunity disorders (63%) and other and unspecified benign neoplasm (58%) with statistical significance compared with the other clusters (all p < 0.05).The immunomarker-driven clustering method could recognise more clinically relevant subgroups of the SADs and would provide a more precise diagnosis basis.