论文标题
使用基因表达数据的全身性红斑狼疮患者分层，以揭示不同免疫途径的表达
Stratification of Systemic Lupus Erythematosus Patients Using Gene Expression Data to Reveal Expression of Distinct Immune Pathways
论文作者
论文摘要
全身性红斑狼疮（SLE）是美国15-24岁的女性死亡的第十个主要原因。在SLE患者中表达的症状和免疫途径的多样性在治疗SLE和新临床试验中造成困难。这项研究对成人SLE患者的基因表达数据进行了无监督的学习，将患者分为簇。通过三种单独的方法（PCA，UMAP和一个简单的线性自动编码器）降低了基因表达数据的维度，并且每种方法的结果都用于将患者分为六个具有K均值聚类的簇。 簇显示了导致SLE的SLE患者的三个独立的免疫途径。这些途径是：（1）高干扰素水平，（2）高自身抗体水平和（3）线粒体凋亡途径的失调。前两个途径在SLE中进行了广泛的研究。然而，在我们的最佳知识中，尚未对线粒体细胞凋亡作为独立的SLE，独立于自身抗体产生的原因，这表明线粒体蛋白可以在未来的研究中为SLE带来一套新的SLE治疗靶标。
Systemic lupus erythematosus (SLE) is the tenth leading cause of death in females 15-24 years old in the US. The diversity of symptoms and immune pathways expressed in SLE patients causes difficulties in treating SLE as well as in new clinical trials. This study used unsupervised learning on gene expression data from adult SLE patients to separate patients into clusters. The dimensionality of the gene expression data was reduced by three separate methods (PCA, UMAP, and a simple linear autoencoder) and the results from each of these methods were used to separate patients into six clusters with k-means clustering. The clusters revealed three separate immune pathways in the SLE patients that caused SLE. These pathways were: (1) high interferon levels, (2) high autoantibody levels, and (3) dysregulation of the mitochondrial apoptosis pathway. The first two pathways have been extensively studied in SLE. However, mitochondrial apoptosis has not been investigated before to the best of our knowledge as a standalone cause of SLE, independent of autoantibody production, indicating that mitochondrial proteins could lead to a new set of therapeutic targets for SLE in future research.
