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Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in

BACKGROUND: Intracranial aneurysm (IA) is a common cerebrovascular disease. The immune mechanism of IA is more complicated, and it is unclear so far. Therefore, it is necessary to continue to explore the immune related molecular mechanism of IA. METHODS: All data were downloaded from the public data...

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Autores principales: Ma, Zhengfei, Zhong, Ping, Yue, Peidong, Sun, Zhongwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088219/
https://www.ncbi.nlm.nih.gov/pubmed/37041519
http://dx.doi.org/10.1186/s12863-023-01121-w
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author Ma, Zhengfei
Zhong, Ping
Yue, Peidong
Sun, Zhongwu
author_facet Ma, Zhengfei
Zhong, Ping
Yue, Peidong
Sun, Zhongwu
author_sort Ma, Zhengfei
collection PubMed
description BACKGROUND: Intracranial aneurysm (IA) is a common cerebrovascular disease. The immune mechanism of IA is more complicated, and it is unclear so far. Therefore, it is necessary to continue to explore the immune related molecular mechanism of IA. METHODS: All data were downloaded from the public database. Limma package and ssGSEA algorithm was used to identify differentially expressed mRNAs (DEmRNAs) and analyze immune cell infiltration, respectively. Machine learning and cytoscape-cytohubba plug-in was used to identify key immune types and multicentric DEmRNAs of IA, respectively. Multicentric DEmRNAs related to key immune cells were screened out as key DEmRNAs by Spearman correlation analysis. Diagnostic models, competing endogenous RNA (ceRNA) regulatory network and transcription factor regulatory network were constructed based on key DEmRNAs. Meanwhile, drugs related to key DEmRNAs were screened out based on DGIdb database. The expression of key DEmRNAs was also verified by real time-PCR. RESULTS: In this study, 7 key DEmRNAs (NRXN1, GRIA2, SLC1A2, SLC17A7, IL6, VEGFA and SYP) associated with key differential immune cell infiltration (CD56bright natural killer cell, Immature B cell and Type 1 T helper cell) were identified. Functional enrichment analysis showed that VEGFA and IL6 may be involved in the regulation of the PI3K-Akt signaling pathway. Moreover, IL6 was also found to be enriched in cytokine-cytokine receptor interaction signaling pathway. In the ceRNA regulatory network, a large number of miRNAs and lncRNAs were found. In the transcription factor regulatory network, the transcription factor SP1 was correlated with VEGFA, SYP and IL6. It is also predicted that drugs related to key DEmRNAs such as CARBOPLATIN, FENTANYL and CILOSTAZOL may contribute to the treatment of IA. In addition, it was also found that SVM and RF models based on key DEmRNAs may be potential markers for diagnosing IA and unruptured intracranial aneurysm (UIA), respectively. The expression trend of key DEmRNAs verified by real-time PCR was consistent with the bioinformatics analysis results. CONCLUSION: The identification of molecules and pathways in this study provides a theoretical basis for understanding the immune related molecular mechanism of IA. Meanwhile, the drug prediction and diagnosis model construction may also be helpful for clinical diagnosis and management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12863-023-01121-w.
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spelling pubmed-100882192023-04-12 Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in Ma, Zhengfei Zhong, Ping Yue, Peidong Sun, Zhongwu BMC Genom Data Research BACKGROUND: Intracranial aneurysm (IA) is a common cerebrovascular disease. The immune mechanism of IA is more complicated, and it is unclear so far. Therefore, it is necessary to continue to explore the immune related molecular mechanism of IA. METHODS: All data were downloaded from the public database. Limma package and ssGSEA algorithm was used to identify differentially expressed mRNAs (DEmRNAs) and analyze immune cell infiltration, respectively. Machine learning and cytoscape-cytohubba plug-in was used to identify key immune types and multicentric DEmRNAs of IA, respectively. Multicentric DEmRNAs related to key immune cells were screened out as key DEmRNAs by Spearman correlation analysis. Diagnostic models, competing endogenous RNA (ceRNA) regulatory network and transcription factor regulatory network were constructed based on key DEmRNAs. Meanwhile, drugs related to key DEmRNAs were screened out based on DGIdb database. The expression of key DEmRNAs was also verified by real time-PCR. RESULTS: In this study, 7 key DEmRNAs (NRXN1, GRIA2, SLC1A2, SLC17A7, IL6, VEGFA and SYP) associated with key differential immune cell infiltration (CD56bright natural killer cell, Immature B cell and Type 1 T helper cell) were identified. Functional enrichment analysis showed that VEGFA and IL6 may be involved in the regulation of the PI3K-Akt signaling pathway. Moreover, IL6 was also found to be enriched in cytokine-cytokine receptor interaction signaling pathway. In the ceRNA regulatory network, a large number of miRNAs and lncRNAs were found. In the transcription factor regulatory network, the transcription factor SP1 was correlated with VEGFA, SYP and IL6. It is also predicted that drugs related to key DEmRNAs such as CARBOPLATIN, FENTANYL and CILOSTAZOL may contribute to the treatment of IA. In addition, it was also found that SVM and RF models based on key DEmRNAs may be potential markers for diagnosing IA and unruptured intracranial aneurysm (UIA), respectively. The expression trend of key DEmRNAs verified by real-time PCR was consistent with the bioinformatics analysis results. CONCLUSION: The identification of molecules and pathways in this study provides a theoretical basis for understanding the immune related molecular mechanism of IA. Meanwhile, the drug prediction and diagnosis model construction may also be helpful for clinical diagnosis and management. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12863-023-01121-w. BioMed Central 2023-04-11 /pmc/articles/PMC10088219/ /pubmed/37041519 http://dx.doi.org/10.1186/s12863-023-01121-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ma, Zhengfei
Zhong, Ping
Yue, Peidong
Sun, Zhongwu
Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in
title Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in
title_full Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in
title_fullStr Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in
title_full_unstemmed Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in
title_short Identification of immune-related molecular markers in intracranial aneurysm (IA) based on machine learning and cytoscape-cytohubba plug-in
title_sort identification of immune-related molecular markers in intracranial aneurysm (ia) based on machine learning and cytoscape-cytohubba plug-in
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088219/
https://www.ncbi.nlm.nih.gov/pubmed/37041519
http://dx.doi.org/10.1186/s12863-023-01121-w
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