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| Status |
Public on Nov 26, 2018 |
| Title |
RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background and Purpose—Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries.
Methods—We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other.
Results—We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. Conclusions—For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture.
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| Overall design |
RNA sequencing of 44 intracranial aneurysm samples (including 21 unruptured, 22 ruptured and 1 undetermined) and 16 control samples of the intracranial cortical artery
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| Contributor(s) |
Kleinloog R, Verweij BH, van der Vlies P, Deelen P, Schwertz MA, de Muynck L, van Damme P, Giuliani F, Regli L, van der Zwan A, Berkelbach van der Sprenke JW, Han KS, Gosselaar P, van Rijen PC, Korkmaz E, Post JA, Rinkel GJ, Veldink JH, Ruigrok YM |
| Citation(s) |
27026628 |
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| Submission date |
Nov 25, 2018 |
| Last update date |
Oct 27, 2022 |
| Contact name |
Ynte Ruigrok |
| E-mail(s) |
ij.m.ruigrok@umcutrecht.nl
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| Organization name |
UMC Utrecht
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| Street address |
Heidelberglaan 100
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| City |
Utrecht |
| ZIP/Postal code |
3584 CX |
| Country |
Netherlands |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (60)
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| Relations |
| BioProject |
PRJNA506840 |
| SRA |
SRP170629 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE122897_readCounts_raw.txt.gz |
2.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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