Dysregulated Gene Expression in Lymphoblasts from Parkinson’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participant Cohort
2.2. Transcriptomic Cohort
2.3. Proteomic Cohort
2.4. Generation of Lymphoblastoid Cell Lines
2.5. Whole-Cell Protein Extraction and Mass Spectrometry
2.6. RNA Extraction and RNA-Seq
2.7. Software Programs and Statistical Analysis
3. Results
3.1. Global Changes in Parkinson Disease Proteomes and Transcriptomes
3.2. Cellular Component
3.3. Dysregulated Proteome
3.4. Dysregulated Transcriptome
3.5. Analysis of Altered GO Biological Processes in Differentially Expressed Transcripts and Proteins in PD Cell Lines
3.6. Dysregulated Proteome
3.7. Dysregulated Transcriptome
3.8. Analysis of Mitochondrial Proteins
3.9. Dysregulated Mitochondrial Proteome
3.10. Dysregulated Transcriptome-Encoding Mitochondrial Proteins
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Complex | Proteins Upregulated (Average Fold-Change) | Proteins Downregulated (Average Fold-Change) | Proportion Test (Significance p-Value) | t-Test (Significance p-Value) |
---|---|---|---|---|
Complex V | 2 (1.65) | 10 (0.85) | 0.04 | 0.45 |
Complex IV | 7 (1.70) | 3 (0.86) | 0.18 | 0.021 |
Complex III | 6 (2.24) | 3 (0.78) | 0.35 | 0.11 |
Complex II | 2 (1.26) | 0 | 0.32 | 0.054 |
Complex I | 19 (2.63) | 7 (0.79) | 0.0023 | 7.86 × 10−4 |
TCA | 17 (1.8) | 7 (0.92) | 0.0094 | 0.0168 |
Mitochondrial transport (TIMM/TOMM complex) | 7 (1.99) | 2 (0.54) | 0.059 | 0.0509 |
SLC25 transporters | 6 (5.02) | 5 (0.91) | 1 | 0.103 |
Others | LAMTOR (1.88), PRKAA1 (2.4), OXA1L (0.69) (Assembly of CV & CIV), IF1 which inhibits ATP activity (4.0) |
Transcripts Upregulated (Average Fold-Change) | Transcripts Downregulated (Average Fold-Change) | Proportion Test (Significance p-Value) | t-Test (Significance p-Value) | |
---|---|---|---|---|
Complex I | 10 (1.04) | 34 (0.91) | 9.41 × 10−7 | 3.94 × 10−6 |
Complex II | 2 (1.02) | 6 (0.90) | 0.13 | 9.01 × 10−3 |
Complex III | 1 (1.10) | 10 (0.89) | 6.47 × 10−4 | 3.96 ×10−3 |
Complex IV | 10 (1.07) | 25 (0.90) | 8.18 × 10−4 | 5.41 × 10−3 |
Complex V | 3 (1.08) | 16 (0.90) | 9.89 × 10−5 | 8.41 × 10−4 |
TCA | 7 (1.08) | 11 (0.94) | 0.32 | 0.40 |
SLC25 transporters | 18 (1.34) | 34 (0.91) | 0.0033 | 0.83 |
TIMM/TOMM | 4 (1.05) | 19 (0.91) | 7.11 × 10−5 | 1.50 × 10−3 |
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Annesley, S.J.; Allan, C.Y.; Sanislav, O.; Evans, A.; Fisher, P.R. Dysregulated Gene Expression in Lymphoblasts from Parkinson’s Disease. Proteomes 2022, 10, 20. https://doi.org/10.3390/proteomes10020020
Annesley SJ, Allan CY, Sanislav O, Evans A, Fisher PR. Dysregulated Gene Expression in Lymphoblasts from Parkinson’s Disease. Proteomes. 2022; 10(2):20. https://doi.org/10.3390/proteomes10020020
Chicago/Turabian StyleAnnesley, Sarah Jane, Claire Yvonne Allan, Oana Sanislav, Andrew Evans, and Paul Robert Fisher. 2022. "Dysregulated Gene Expression in Lymphoblasts from Parkinson’s Disease" Proteomes 10, no. 2: 20. https://doi.org/10.3390/proteomes10020020