Work

The SjD Map: an interactive pathway tour into Sjögren’s disease signalling mechanisms

Year: 2026

Type: article

Abstract: Objectives Sjögren’s disease (SjD) remains a major unmet medical challenge, marked by biological complexity, patient heterogeneity, and a lack of curative treatments. To advance the understanding of its pathogenesis and support therapeutic discovery, we developed a comprehensive knowledgebase in the form of a Molecular Interaction Map (MIM). Methods Differential expression analysis was performed on peripheral blood samples from SjD patients and healthy controls across three datasets: GSE51092 (190 SjD vs 32 controls), UKPSSR (151 SjD vs 29 controls) and PRECISESADS (304 SjD vs 341 controls). Pathway enrichment analyses provided guidance for MIM construction, which was further refined through literature mining to integrate data-driven results with curated knowledge. Results A total of 1,625 differentially expressed genes (DEGs) were identified: 725 from PRECISESADS, 1,162 from GSE51092, and 239 from UKPSSR, with 25 DEGs shared across all three datasets. Among these, nine common DEGs were associated with interferon signalling, reinforcing experimental evidence pointing to its pivotal role in SjD. Enrichment analyses revealed 146 pathways, 43 of which were successfully incorporated into the MIM. The resulting SjD Map freely accessible at https://sjdmap.elixir-luxembourg.org/ , comprises 829 molecular entities connected by 598 interactions, with 45% of the information depicted supported by transcriptomic data and 47% derived from literature. The map also includes overlays of experimental data and clinical trial information. Conclusion This first comprehensive Sjögren’s Disease Map, developed through a hybrid data-driven and literature-based approach, offers an integrative view of SjD pathogenesis. It supports visualisation of mechanistic pathways, omics-based data overlays, enables incorporation of user data and drug queries. Abstract Figure Graphical abstract Key messages This is the first molecular interaction map specific of Sjögren’s Disease It enables comprehensive visualisation of affected pathways through integrated transcriptomic and literature-based evidence, following system’s biology graphical notation schemes The map may support therapeutic discovery by linking molecular mechanisms to clinical data and drug targets

Source: npj Systems Biology and Applications

DOI: 10.1038/s41540-026-00670-x