Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder. Various evidence has revealed the possible penetration of peripheral immune cells in the substantia nigra, which may be essential for PD. Our study uses machine learning (ML) to screen for potential PD genetic biomarkers. G...

Full description

Bibliographic Details
Main Authors: Yiwen Bao, Lufeng Wang, Fei Yu, Jie Yang, Dongya Huang
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/13/2/175
_version_ 1797622056320237568
author Yiwen Bao
Lufeng Wang
Fei Yu
Jie Yang
Dongya Huang
author_facet Yiwen Bao
Lufeng Wang
Fei Yu
Jie Yang
Dongya Huang
author_sort Yiwen Bao
collection DOAJ
description Parkinson’s disease (PD) is a common progressive neurodegenerative disorder. Various evidence has revealed the possible penetration of peripheral immune cells in the substantia nigra, which may be essential for PD. Our study uses machine learning (ML) to screen for potential PD genetic biomarkers. Gene expression profiles were screened from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) were selected for the enrichment analysis. A protein–protein interaction (PPI) network was built with the STRING database (Search Tool for the Retrieval of Interacting Genes), and two ML approaches, namely least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), were employed to identify candidate genes. The external validation dataset further tested the expression degree and diagnostic value of candidate biomarkers. To assess the validity of the diagnosis, we determined the receiver operating characteristic (ROC) curve. A convolution tool was employed to evaluate the composition of immune cells by CIBERSORT, and we performed correlation analyses on the basis of the training dataset. Twenty-seven DEGs were screened in the PD and control samples. Our results from the enrichment analysis showed a close association with inflammatory and immune-associated diseases. Both the LASSO and SVM algorithms screened eight and six characteristic genes. AGTR1, GBE1, TPBG, and HSPA6 are overlapping hub genes strongly related to PD. Our results of the area under the ROC (AUC), including AGTR1 (AUC = 0.933), GBE1 (AUC = 0.967), TPBG (AUC = 0.767), and HSPA6 (AUC = 0.633), suggested that these genes have good diagnostic value, and these genes were significantly associated with the degree of immune cell infiltration. AGTR1, GBE1, TPBG, and HSPA6 were identified as potential biomarkers in the diagnosis of PD and provide a novel viewpoint for further study on PD immune mechanism and therapy.
first_indexed 2024-03-11T09:04:52Z
format Article
id doaj.art-4a29e2abf50343b68fa211b496a16946
institution Directory Open Access Journal
issn 2076-3425
language English
last_indexed 2024-03-11T09:04:52Z
publishDate 2023-01-01
publisher MDPI AG
record_format Article
series Brain Sciences
spelling doaj.art-4a29e2abf50343b68fa211b496a169462023-11-16T19:27:14ZengMDPI AGBrain Sciences2076-34252023-01-0113217510.3390/brainsci13020175Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM AlgorithmsYiwen Bao0Lufeng Wang1Fei Yu2Jie Yang3Dongya Huang4Tongji University School of Medicine, East Hospital, Department of Neurology, Tongji University, Shanghai 200070, ChinaTongji University School of Medicine, East Hospital, Department of Neurology, Tongji University, Shanghai 200070, ChinaTongji University School of Medicine, East Hospital, Department of Neurology, Tongji University, Shanghai 200070, ChinaTongji University School of Medicine, East Hospital, Department of Neurology, Tongji University, Shanghai 200070, ChinaTongji University School of Medicine, East Hospital, Department of Neurology, Tongji University, Shanghai 200070, ChinaParkinson’s disease (PD) is a common progressive neurodegenerative disorder. Various evidence has revealed the possible penetration of peripheral immune cells in the substantia nigra, which may be essential for PD. Our study uses machine learning (ML) to screen for potential PD genetic biomarkers. Gene expression profiles were screened from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) were selected for the enrichment analysis. A protein–protein interaction (PPI) network was built with the STRING database (Search Tool for the Retrieval of Interacting Genes), and two ML approaches, namely least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), were employed to identify candidate genes. The external validation dataset further tested the expression degree and diagnostic value of candidate biomarkers. To assess the validity of the diagnosis, we determined the receiver operating characteristic (ROC) curve. A convolution tool was employed to evaluate the composition of immune cells by CIBERSORT, and we performed correlation analyses on the basis of the training dataset. Twenty-seven DEGs were screened in the PD and control samples. Our results from the enrichment analysis showed a close association with inflammatory and immune-associated diseases. Both the LASSO and SVM algorithms screened eight and six characteristic genes. AGTR1, GBE1, TPBG, and HSPA6 are overlapping hub genes strongly related to PD. Our results of the area under the ROC (AUC), including AGTR1 (AUC = 0.933), GBE1 (AUC = 0.967), TPBG (AUC = 0.767), and HSPA6 (AUC = 0.633), suggested that these genes have good diagnostic value, and these genes were significantly associated with the degree of immune cell infiltration. AGTR1, GBE1, TPBG, and HSPA6 were identified as potential biomarkers in the diagnosis of PD and provide a novel viewpoint for further study on PD immune mechanism and therapy.https://www.mdpi.com/2076-3425/13/2/175Parkinson’s diseaseimmune infiltratesleast absolute shrinkage and selection operatorsupport vector machine
spellingShingle Yiwen Bao
Lufeng Wang
Fei Yu
Jie Yang
Dongya Huang
Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms
Brain Sciences
Parkinson’s disease
immune infiltrates
least absolute shrinkage and selection operator
support vector machine
title Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms
title_full Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms
title_fullStr Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms
title_full_unstemmed Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms
title_short Parkinson’s Disease Gene Biomarkers Screened by the LASSO and SVM Algorithms
title_sort parkinson s disease gene biomarkers screened by the lasso and svm algorithms
topic Parkinson’s disease
immune infiltrates
least absolute shrinkage and selection operator
support vector machine
url https://www.mdpi.com/2076-3425/13/2/175
work_keys_str_mv AT yiwenbao parkinsonsdiseasegenebiomarkersscreenedbythelassoandsvmalgorithms
AT lufengwang parkinsonsdiseasegenebiomarkersscreenedbythelassoandsvmalgorithms
AT feiyu parkinsonsdiseasegenebiomarkersscreenedbythelassoandsvmalgorithms
AT jieyang parkinsonsdiseasegenebiomarkersscreenedbythelassoandsvmalgorithms
AT dongyahuang parkinsonsdiseasegenebiomarkersscreenedbythelassoandsvmalgorithms