ArticlePloS one2019
Microenvironment of ruptured cerebral aneurysms discovered using data driven analysis of gene expression.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Review
- Epithelial-mesenchymal transition related genes in unruptured aneurysms identified through weighted gene coexpression network analysis.Scientific reports · 2022Article
- Integrated computational analyses reveal novel insights into the stromal microenvironment of SHH-subtype medulloblastoma.Scientific reports · 2021Article
- Identification and validation of key genes mediating intracranial aneurysm rupture by weighted correlation network analysis.Annals of translational medicine · 2020Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt is well known that ruptured intracranial aneurysms are associated with substantial morbidity and mortality, yet our understanding of the genetic mechanisms of rupture remains poor. We hypothesize that applying novel techniques to the genetic analysis of aneurysmal tissue will yield key rupture-associated mechanisms and novel drug candidates for the prevention of rupture.
methodsWe applied weighted gene co-expression networks (WGCNA) and population-specific gene expression analysis (PSEA) to transcriptomic data from 33 ruptured and unruptured aneurysm domes. Mechanisms were annotated using Gene Ontology, and gene network/population-specific expression levels correlated with rupture state. We then used computational drug repurposing to identify plausible drug candidates for the prevention of aneurysm rupture.
resultsNetwork analysis of bulk tissue identified multiple immune mechanisms to be associated with aneurysm rupture. Targeting these processes with computational drug repurposing revealed multiple candidates for preventing rupture including Btk inhibitors and modulators of hypoxia inducible factor. In the macrophage-specific analysis, we identify rupture-associated mechanisms MHCII antigen processing, cholesterol efflux, and keratan sulfate catabolism. These processes map well onto several of highly ranked drug candidates, providing further validation.
conclusionsOur results are the first to demonstrate population-specific expression levels and intracranial aneurysm rupture, and propose novel drug candidates based on network-based transcriptomics.
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