Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene co-expression network analysis

Du, Guojia; Geng, Deqin; Zhou, Kai; Fan, Yandong; Su, Riqing; Zhou, Qina; Liu, Bo; Duysenbi, Serick

doi:10.1080/21691401.2020.1770264

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…Further investigation was also conducted on enrichment analysis of different types of aneurysms. In GO enrichment analysis, we found SNPs of gut microbiomes that were suggestively associated with IA were enriched in cAMP signaling pathway, which were probably related to the formation and rupture of IA ( Du et al, 2020 ); while voltage-gated monoatomic cation channels, such as K + and Ca + channels, were reported to be associated with cerebral vasospasm after the rupture of IA ( Cataldi, 2013 ; Koide and Wellman, 2013 ). In addition, the regulation of hormone levels was associated with AAA in GO enrichment analysis.…”

Section: Discussionmentioning

confidence: 99%

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Qiu,

Hou,

Wei

et al. 2024

Front. Microbiol.

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BackgroundPrevious studies suggests that gut microbiomes are associated with the formation and progression of aneurysms. However, the causal association between them remains unclear.MethodsA two-sample Mendelian randomization was conducted to investigate whether gut microbiomes have a causal effect on the risk of intracerebral aneurysm (IA), thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA), and aortic aneurysm (AA). Single nucleotide polymorphisms (SNPs) smaller than the locus-wide significance level (1 × 10−5) were selected as instrumental variables. We used inverse-variance weighted (IVW) test as the primary method for the evaluation of causal association. MR-Egger, weighted median, weighted mode, and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods were conducted for sensitive analysis. The p-value was adjusted by the false discovery rate (FDR) which adjust the results of multiple comparisons, a p < 0.05 and q < 0.1 was considered a significant causal association. Additionally, a p < 0.05 and q > 0.1 was considered a suggestive causal effect. Additionally, reverse MR was also performed to exclude the possibility of reverse causality.ResultsThe phylum Firmicutes (OR = 0.62; 95% CI, 0.48–0.81), class Lentisphaeria (OR = 0.75; 95% CI, 0.62–0.89), and order Victivallales (OR = 0.75; 95% CI, 0.62–0.89) have a causal protective effect on the risk of AAA. Additionally, class Verrucomicrobia, class Deltaproteobacteria, order Verrucomicrobiale, family Verrucomicrobiacea, genus Eubacterium rectale group, genus Akkermansia, and genus Clostridium innocuum group were negatively associated with the risk of different types of aneurysms, whereas class Negativicutes, order Selenomonadales, and genus Roseburia had positive causal association with different types of aneurysms (p < 0.05; q > 0.1). Further sensitivity analysis validated the robustness of our MR results, and no reverse causality was found with these gut microbiomes (p > 0.05).ConclusionOur MR analysis confirmed the causal association of specific gut microbiomes with AAA, and these microbiomes were considered as protective factors. Our result may provide novel insights and theoretical basis for the prevention of aneurysms through regulation of gut microbiomes.

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Section: Discussionmentioning

confidence: 99%

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Qiu,

Hou,

Wei

et al. 2024

Front. Microbiol.

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“…Although such efforts are of great value, they do not assay the aneurysm tissue specifically for the local gene expression alterations. Small series have described the gene expression profiles from the aneurysmal domes collected as part of clipping ( 35 , 40 , 41 ); however, this type of assay is not possible for those aneurysms not amenable to open surgical treatment (similar to most fusiform vertebrobasilar aneurysms). With this manuscript, we advance the concept of endovascular biopsy and scRNAseq as a next step toward a precision medicine approach to neurovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Narsinh

McCoy

et al. 2021

Front. Neurol.

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Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa.Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis.Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα.Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.

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“…Along with the development of bioinformatic tools appeared a new type of study presenting re-analyzed data from available datasets, including expression data from the Gene Expression Omnibus (GEO). Approximately one third of these published secondary analyses utilized a single dataset [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ] and two thirds leveraged data from two to eight datasets [ 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 ]. These studies did not provide any new additional clinical data but rather aimed to deepen the insight into molecular mechanisms of the IA pathophysiology by revealing key regulatory networks and interactions between investigated molecules.…”

Section: Studies Based On Existing Datasetsmentioning

confidence: 99%

Transcriptomic Studies on Intracranial Aneurysms

Morga¹,

Pera

2023

Genes

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Intracranial aneurysm (IA) is a relatively common vascular malformation of an intracranial artery. In most cases, its presence is asymptomatic, but IA rupture causing subarachnoid hemorrhage is a life-threating condition with very high mortality and disability rates. Despite intensive studies, molecular mechanisms underlying the pathophysiology of IA formation, growth, and rupture remain poorly understood. There are no specific biomarkers of IA presence or rupture. Analysis of expression of mRNA and other RNA types offers a deeper insight into IA pathobiology. Here, we present results of published human studies on IA-focused transcriptomics.

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Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene co-expression network analysis

Abstract: Duysenbi (2020) Identification of potential key pathways, genes and circulating markers in the development of intracranial aneurysm based on weighted gene coexpression network analysis,

Cited by 6 publications

References 41 publications

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Causal association between gut microbiomes and different types of aneurysms: a Mendelian randomization study

Endovascular Biopsy of Vertebrobasilar Aneurysm in Patient With Polyarteritis Nodosa

Transcriptomic Studies on Intracranial Aneurysms

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