Stratification of Systemic Lupus Erythematosus Patients with Gene Expression Data Reveals Expression of Distinct Immune Pathways

Abstract

AbstractSystemic 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. Mitochondrial apoptosis has not been investigated before to our knowledge as a standalone cause of SLE, independent of autoantibody production, and mitochondrial proteins could be investigated as a therapeutic target for SLE in the future.