Integrated machine learning framework identifies EPSTI1 as a key diagnostic biomarker for Sjögren's disease:
Jianbin Li1,2, Renhe Li1,2, Wenwen Wang1,2
1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Clinical Rheumatology
|July 10, 2026
Summary
This study developed a 14-gene signature for diagnosing Sjögren's disease (SjD) using machine learning. EPSTI1 was identified as a key biomarker, primarily expressed in myeloid cells, showing potential for precise SjD diagnosis.
Area of Science:
- Immunology
- Genomics
- Computational Biology
Background:
- Sjögren's disease (SjD) diagnosis relies on clinical and serological criteria, lacking robust molecular signatures.
- Transcriptomic analysis offers potential for identifying objective biomarkers for SjD.
Purpose of the Study:
- To develop a transcriptomic diagnostic signature for Sjögren's disease (SjD) using machine learning.
- To identify and functionally characterize key SjD biomarker genes, including EPSTI1.
- To investigate the cellular and molecular mechanisms underlying SjD pathogenesis.
Main Methods:
- Integrated analysis of multiple peripheral blood transcriptomic datasets for training and validation.
- Systematic evaluation of 113 machine learning algorithm combinations for diagnostic signature development.
- Single-cell RNA sequencing, SHAP analysis, pathway enrichment, and RT-qPCR for biomarker characterization.
Main Results:
- A 14-gene diagnostic signature achieved high performance (AUC > 0.87) across independent cohorts.
- EPSTI1 was identified as the top diagnostic biomarker, correlating with SjD clinical markers.
- Single-cell analysis localized EPSTI1 expression to monocytes and dendritic cells, implicating myeloid cells in SjD.
Conclusions:
- An integrated machine learning framework identified a robust 14-gene signature for SjD diagnosis.
- EPSTI1 is a promising diagnostic biomarker for SjD, predominantly expressed in myeloid cells.
- Further prospective studies are warranted to confirm EPSTI1's clinical utility in larger SjD cohorts.
