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Integrated systems analysis of salivary gland transcriptomics reveals key molecular networks in Sjögren’s syndrome

Overview of attention for article published in Arthritis Research & Therapy, December 2019
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Title
Integrated systems analysis of salivary gland transcriptomics reveals key molecular networks in Sjögren’s syndrome
Published in
Arthritis Research & Therapy, December 2019
DOI 10.1186/s13075-019-2082-9
Pubmed ID
Authors

Hong Ki Min, Su-Jin Moon, Kyung-Su Park, Ki-Jo Kim

Abstract

Treatment of patients with Sjögren's syndrome (SjS) is a clinical challenge with high unmet needs. Gene expression profiling and integrative network-based approaches to complex disease can offer an insight on molecular characteristics in the context of clinical setting. An integrated dataset was created from salivary gland samples of 30 SjS patients. Pathway-driven enrichment profiles made by gene set enrichment analysis were categorized using hierarchical clustering. Differentially expressed genes (DEGs) were subjected to functional network analysis, where the elements of the core subnetwork were used for key driver analysis. We identified 310 upregulated DEGs, including nine known genetic risk factors and two potential biomarkers. The core subnetwork was enriched with the processes associated with B cell hyperactivity. Pathway-based subgrouping revealed two clusters with distinct molecular signatures for the relevant pathways and cell subsets. Cluster 2, with low-grade inflammation, showed a better response to rituximab therapy than cluster 1, with high-grade inflammation. Fourteen key driver genes appeared to be essential signaling mediators downstream of the B cell receptor (BCR) signaling pathway and to have a positive relationship with histopathology scores. Integrative network-based approaches provide deep insights into the modules and pathways causally related to SjS and allow identification of key targets for disease. Intervention adjusted to the molecular traits of the disease would allow the achievement of better outcomes, and the BCR signaling pathway and its leading players are promising therapeutic targets.

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Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 December 2019.
All research outputs
#11,038,393
of 14,533,262 outputs
Outputs from Arthritis Research & Therapy
#1,872
of 2,320 outputs
Outputs of similar age
#213,375
of 318,455 outputs
Outputs of similar age from Arthritis Research & Therapy
#188
of 227 outputs
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