Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease

Background: Parkinson’s disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases.Methods: This study aimed to identify potential novel biomarkers of Parkinson’s diseas...

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Main Authors: Songyun Zhao, Li Zhang, Wei Ji, Yachen Shi, Guichuan Lai, Hao Chi, Weiyi Huang, Chao Cheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.1010361/full
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author Songyun Zhao
Li Zhang
Wei Ji
Yachen Shi
Guichuan Lai
Hao Chi
Weiyi Huang
Chao Cheng
author_facet Songyun Zhao
Li Zhang
Wei Ji
Yachen Shi
Guichuan Lai
Hao Chi
Weiyi Huang
Chao Cheng
author_sort Songyun Zhao
collection DOAJ
description Background: Parkinson’s disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases.Methods: This study aimed to identify potential novel biomarkers of Parkinson’s disease by biomarker analysis and to explore immune cell infiltration during the onset of cuprotosis. Gene expression profiles were retrieved from the GEO database for the GSE8397, GSE7621, GSE20163, and GSE20186 datasets. Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG). Immune cell infiltration was estimated by ssGSEA, and cuprotosis-related genes associated with immune cells and immune function were examined using spearman correlation analysis. Nomogram was created to validate the accuracy of these cuprotosis-related genes in predicting PD disease progression. Classification of Parkinson’s specimens using consensus clustering methods.Result: Three PD datasets from the Gene Expression Omnibus (GEO) database were combined after eliminating batch effects. By ssGSEA, we identified three cuprotosis-related genes ATP7A, SLC31A1, and DBT associated with immune cells or immune function in PD and more accurate for the diagnosis of Parkinson’s disease course. Patients could benefit clinically from a characteristic line graph based on these genes. Consistent clustering analysis identified two subtypes, with the C2 subtype exhibiting higher immune cell infiltration and immune function.Conclusion: In conclusion, our study reveals that several newly identified cuprotosis-related genes intervene in the progression of Parkinson’s disease through immune cell infiltration.
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spelling doaj.art-89881eeb70a9411ab89daad8b6f14aec2022-12-22T04:36:50ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-10-011310.3389/fgene.2022.10103611010361Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s diseaseSongyun Zhao0Li Zhang1Wei Ji2Yachen Shi3Guichuan Lai4Hao Chi5Weiyi Huang6Chao Cheng7Department of Neurosurgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaDepartment of Neurology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaDepartment of Neurosurgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaDepartment of Neurology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Chongqing, ChinaClinical Medicine College, Southwest Medical University, Luzhou, ChinaDepartment of Neurosurgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaDepartment of Neurosurgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, ChinaBackground: Parkinson’s disease (PD) is a neurodegenerative disease commonly seen in the elderly. On the other hand, cuprotosis is a new copper-dependent type of cell death that can be observed in various diseases.Methods: This study aimed to identify potential novel biomarkers of Parkinson’s disease by biomarker analysis and to explore immune cell infiltration during the onset of cuprotosis. Gene expression profiles were retrieved from the GEO database for the GSE8397, GSE7621, GSE20163, and GSE20186 datasets. Three machine learning algorithms: the least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE) were used to screen for signature genes for Parkinson’s disease onset and cuprotosis-related genes (CRG). Immune cell infiltration was estimated by ssGSEA, and cuprotosis-related genes associated with immune cells and immune function were examined using spearman correlation analysis. Nomogram was created to validate the accuracy of these cuprotosis-related genes in predicting PD disease progression. Classification of Parkinson’s specimens using consensus clustering methods.Result: Three PD datasets from the Gene Expression Omnibus (GEO) database were combined after eliminating batch effects. By ssGSEA, we identified three cuprotosis-related genes ATP7A, SLC31A1, and DBT associated with immune cells or immune function in PD and more accurate for the diagnosis of Parkinson’s disease course. Patients could benefit clinically from a characteristic line graph based on these genes. Consistent clustering analysis identified two subtypes, with the C2 subtype exhibiting higher immune cell infiltration and immune function.Conclusion: In conclusion, our study reveals that several newly identified cuprotosis-related genes intervene in the progression of Parkinson’s disease through immune cell infiltration.https://www.frontiersin.org/articles/10.3389/fgene.2022.1010361/fullPDcuprotosisimmune cell infiltrationconsensus clusteringbioinformatics analysis
spellingShingle Songyun Zhao
Li Zhang
Wei Ji
Yachen Shi
Guichuan Lai
Hao Chi
Weiyi Huang
Chao Cheng
Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
Frontiers in Genetics
PD
cuprotosis
immune cell infiltration
consensus clustering
bioinformatics analysis
title Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
title_full Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
title_fullStr Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
title_full_unstemmed Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
title_short Machine learning-based characterization of cuprotosis-related biomarkers and immune infiltration in Parkinson’s disease
title_sort machine learning based characterization of cuprotosis related biomarkers and immune infiltration in parkinson s disease
topic PD
cuprotosis
immune cell infiltration
consensus clustering
bioinformatics analysis
url https://www.frontiersin.org/articles/10.3389/fgene.2022.1010361/full
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