Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease
Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by an insidious onset. Despite the emphasis on motor symptom-based diagnosis, there remains an unmet clinical need for effective diagnostic approaches during the prodromal phase of PD. Recent advances in sing...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-80185-9 |
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| author | Lin Wang Yidan Qin Jia Song Jing Xu Wei Quan Hang Su Huibin Zeng Jian Zhang Jia Li Jiajun Chen |
| author_facet | Lin Wang Yidan Qin Jia Song Jing Xu Wei Quan Hang Su Huibin Zeng Jian Zhang Jia Li Jiajun Chen |
| author_sort | Lin Wang |
| collection | DOAJ |
| description | Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by an insidious onset. Despite the emphasis on motor symptom-based diagnosis, there remains an unmet clinical need for effective diagnostic approaches during the prodromal phase of PD. Recent advances in single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic analyses of PD patients open avenues for identifying potential diagnostic biomarkers. A comprehensive cell trajectory analysis was conducted using scRNA-seq datasets to identify gene expressions associated with the cellular transition from healthy to PD-associated states. Integration of scRNA-seq datasets with weighted gene co-expression network analysis (WGCNA) allowed extraction of pyroptosis-associated differentially expressed genes (PDEGs). Using LASSO logistic regression, support vector machine recursive feature elimination (SVM-RFE) and random forest methods, we developed a diagnostic model centred on PDEGs. In addition, immunoinfiltration, inflammatory signalling pathways and intercellular communication were detected by scRNA-seq analyses. In PD patients, the number of cells including metencephalic-like cells, excitatory neurons, inhibitory neurons and MHB-like cells was significantly reduced, whereas the proportion of astrocytes and microglia, immunoinfiltration and inflammatory signalling pathways were upregulated compared to healthy individuals. Using scRNA-seq and WGCNA analyses, two pyroptosis-related diagnostic genes, POLR2K and TIMM8B, were identified and a diagnostic model based on them was constructed, which showed promising performance upon validation. This study established a pyroptosis-related diagnostic model for PD through the analyses of scRNA-seq combined with bulk transcriptome data, which improved the understanding of the role of PDEGs in PD and provided new insights into the diagnostic strategies for this neurodegenerative disease. |
| format | Article |
| id | doaj-art-b6bf45cb6b4d4aa09037e0f88b52e9e1 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b6bf45cb6b4d4aa09037e0f88b52e9e12024-11-24T12:26:18ZengNature PortfolioScientific Reports2045-23222024-11-0114111510.1038/s41598-024-80185-9Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s diseaseLin Wang0Yidan Qin1Jia Song2Jing Xu3Wei Quan4Hang Su5Huibin Zeng6Jian Zhang7Jia Li8Jiajun Chen9Department of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityDepartment of Neurology, China-Japan Union Hospital of Jilin UniversityAbstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by an insidious onset. Despite the emphasis on motor symptom-based diagnosis, there remains an unmet clinical need for effective diagnostic approaches during the prodromal phase of PD. Recent advances in single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic analyses of PD patients open avenues for identifying potential diagnostic biomarkers. A comprehensive cell trajectory analysis was conducted using scRNA-seq datasets to identify gene expressions associated with the cellular transition from healthy to PD-associated states. Integration of scRNA-seq datasets with weighted gene co-expression network analysis (WGCNA) allowed extraction of pyroptosis-associated differentially expressed genes (PDEGs). Using LASSO logistic regression, support vector machine recursive feature elimination (SVM-RFE) and random forest methods, we developed a diagnostic model centred on PDEGs. In addition, immunoinfiltration, inflammatory signalling pathways and intercellular communication were detected by scRNA-seq analyses. In PD patients, the number of cells including metencephalic-like cells, excitatory neurons, inhibitory neurons and MHB-like cells was significantly reduced, whereas the proportion of astrocytes and microglia, immunoinfiltration and inflammatory signalling pathways were upregulated compared to healthy individuals. Using scRNA-seq and WGCNA analyses, two pyroptosis-related diagnostic genes, POLR2K and TIMM8B, were identified and a diagnostic model based on them was constructed, which showed promising performance upon validation. This study established a pyroptosis-related diagnostic model for PD through the analyses of scRNA-seq combined with bulk transcriptome data, which improved the understanding of the role of PDEGs in PD and provided new insights into the diagnostic strategies for this neurodegenerative disease.https://doi.org/10.1038/s41598-024-80185-9Parkinson’s diseaseSingle cell RNA sequencingPyroptosisDiagnostic model |
| spellingShingle | Lin Wang Yidan Qin Jia Song Jing Xu Wei Quan Hang Su Huibin Zeng Jian Zhang Jia Li Jiajun Chen Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease Scientific Reports Parkinson’s disease Single cell RNA sequencing Pyroptosis Diagnostic model |
| title | Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease |
| title_full | Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease |
| title_fullStr | Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease |
| title_full_unstemmed | Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease |
| title_short | Integrated analysis of single-cell RNA sequencing and bulk transcriptome data identifies a pyroptosis-associated diagnostic model for Parkinson’s disease |
| title_sort | integrated analysis of single cell rna sequencing and bulk transcriptome data identifies a pyroptosis associated diagnostic model for parkinson s disease |
| topic | Parkinson’s disease Single cell RNA sequencing Pyroptosis Diagnostic model |
| url | https://doi.org/10.1038/s41598-024-80185-9 |
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