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Updated: Mar 24, 2026

RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells
Published on: February 13, 2013
RNA sequencing-derived gene co-expression and drug-gene interaction analysis reveal STAT1 as a potential therapeutic
Michail Baltsiotis1,2, Kleio-Maria Verrou2, Petros P Sfikakis1,2
1First Department of Propaedeutic Internal Medicine, Joint Academic Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Objective:
Thrombotic primary antiphospholipid syndrome (PAPS) pathogenesis remains undefined, and recurrent thrombosis may occur despite adequate anticoagulation treatment. Identifying disease-specific molecular pathways and regulators can help in the discovery of novel therapeutic targets. Herein, we examine gene co-expression networks and potential druggable targets in thrombotic PAPS.
Methods:
We analyzed a whole-blood RNA-sequencing dataset from 62 well-characterized patients with thrombotic PAPS (40% with recurrent thrombosis), and 29 age/sex-matched healthy controls(HCs). Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify gene modules associated with PAPS, followed by enrichment analysis. Drug-gene interaction analysis of hub regulators within the identified networks was applied. Genes were classified based on target drug annotation and priority categories (low/medium/high).
Results:
WGCNA of whole-blood transcriptome of thrombotic PAPS and HCs, which included 8,190 expressed genes, identified five co-expression modules, two of which correlated with PAPS: the yellow, consisted of 42 genes enriched in immune-related functions, and the brown comprised 144 genes with a regulatory signature enriched in transcription activation pathways. A merged module demonstrated enhanced correlation with PAPS compared with HCs (r=0.221, p=0.035). Both yellow and brown, and merged module, were co-regulated by Transducer and Activator of Transcription 1 (STAT1), which emerged as a central hub gene. STAT1 was also present in 5 of 6 immune-related pathways. In drug-gene interaction analysis, STAT1 was among the four highly-ranked genes, and displayed many interactions and strong pharmacological support.
Conclusion:
STAT1 is identified as a central regulator of gene expression networks in PAPS, integrating both immune-related and regulatory processes. Assessment of pharmacological target availability revealed STAT1 as a promising treatment target.
Insights
STAT1 is a key regulator in thrombotic antiphospholipid syndrome (PAPS), integrating immune and regulatory pathways. This finding highlights STAT1 as a promising therapeutic target for PAPS, potentially improving treatment outcomes.
Area of Science:
- Immunology
- Genomics
- Pharmacology
Background:
- Thrombotic primary antiphospholipid syndrome (PAPS) pathogenesis is not fully understood, and treatment often fails to prevent recurrent thrombosis.
- Identifying specific molecular pathways and drug targets is crucial for developing novel therapies for PAPS.
Purpose of the Study:
- To investigate gene co-expression networks in thrombotic PAPS.
- To identify potential druggable targets and molecular regulators within these networks.
Main Methods:
- Whole-blood RNA sequencing data from 62 PAPS patients and 29 healthy controls were analyzed.
- Weighted Gene Co-expression Network Analysis (WGCNA) identified PAPS-associated gene modules.
- Drug-gene interaction analysis prioritized potential therapeutic targets.
Main Results:
- Two gene modules (yellow and brown) significantly correlated with PAPS, enriched in immune and transcriptional pathways.
- STAT1 (Transducer and Activator of Transcription 1) emerged as a central hub gene, co-regulating both modules.
- STAT1 showed strong pharmacological support and was among the top-ranked druggable targets.
Conclusions:
- STAT1 is a central regulator in PAPS, linking immune and regulatory gene expression.
- STAT1 represents a promising therapeutic target for thrombotic PAPS.
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