Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue
Abstract
:1. Introduction
2. Results
PoMS Analysis and Assignment to Study Groups
3. Multiomics Analysis of Test Group Salivary Exosomes
3.1. Quantitative Global Proteomics on Salivary Exosomes
3.2. Verification of Protein Measurements in Neuron-Derived Exosomes by Targeted MS
3.3. MicroRNA Analysis Using NanoString
3.4. Verification of miRNA Measurements Using qPCR
4. Biomarker Identification in Discovery Group Saliva
Identification of Additional Significantly Altered Protein and miRNA
5. Confirmation of Biomarkers and Fold Change in Validation Group Salivary Exosomes
5.1. Validation of Protein Biomarkers
5.2. Validation of miRNA Biomarkers
5.3. PGK1 Protein and miR3185 in Saliva as Potential Biomarkers of Fatigue
5.4. Integration of Test, Discovery, and Validation Data Reveals Proteins Associated with Work
6. Discussion
7. Methods
7.1. Participants
7.2. Whole Saliva Collection
7.3. The Profile of Mood States (PoMS) Questionnaire
7.4. Separation of Saliva Samples by PoMS TMD Score
7.5. EV Isolation and Enrichment for Exosomes
7.6. Quantitative Global Proteomics Analysis
7.7. Proteomics Analysis
7.8. Protein Bioinformatics Analysis
7.9. Targeted LC-MS/MS Protein Quantification
7.10. Global miRNA Analysis
7.11. Targeted miRNA Analysis
7.12. Identification of miRNA Target Genes
7.13. Statistical Analysis
7.14. Study Design
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Symbol | Protein Description | Protein Fold Change: Post-/Pre-Work | Protein p-Value: Post-/Pre-Work | miRNA | miRNA Fold Change: Post-/Pre-Work | miRNA p-Value: Post-/Pre-Work |
---|---|---|---|---|---|---|
LEG1 | Liver-enriched gene 1 protein | 4.46 | 0.079 | |||
AMY1A | Alpha-amylase 1 n,c | 1.85 | 0.002 | |||
BPIFA2 | BPI fold-containing family A member n | 1.64 | 0.006 | |||
CA6 | Carbonic anhydrase 6 n | 1.5 | 0.083 | |||
PGK1 | Phosphoglycerate kinase 1 n | 1.34 | 0.08 | hsa-miR-3185 | 0.79 | 0.016 |
DPP4 | Dipeptidyl peptidase 4 | 1.24 | 0.03 | |||
SBSN | Suprabasin | −1.23 | 0.06 | |||
PIGR | Polymeric immunoglobulin receptor m,n,c | −1.28 | 0.063 | hsa-miR-642a-5p | 1.9 | 0.04 |
CSTB | Cystatin-B n,c | −1.34 | 0.057 | |||
SPRR3 | Small proline-rich protein 3 | −1.49 | 0.01 | |||
CRABP2 | Cellular retinoic acid-binding protein 2 | −1.49 | 0.098 | |||
FABP5 | Fatty acid-binding protein 5 | −1.72 | 0.004 | |||
YWHAZ | 14-3-3 protein zeta/delta n,c | −2.22 | 0.036 | hsa-miR-134-3p | 1.5 | 0.058 |
DMBT1 | Deleted in malignant brain tumors 1 n,c | −2.63 | 0.027 |
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Cohn, W.; Zhu, C.; Campagna, J.; Bilousova, T.; Spilman, P.; Teter, B.; Li, F.; Guo, R.; Elashoff, D.; Cole, G.M.; et al. Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue. Int. J. Mol. Sci. 2022, 23, 5257. https://doi.org/10.3390/ijms23095257
Cohn W, Zhu C, Campagna J, Bilousova T, Spilman P, Teter B, Li F, Guo R, Elashoff D, Cole GM, et al. Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue. International Journal of Molecular Sciences. 2022; 23(9):5257. https://doi.org/10.3390/ijms23095257
Chicago/Turabian StyleCohn, Whitaker, Chunni Zhu, Jesus Campagna, Tina Bilousova, Patricia Spilman, Bruce Teter, Feng Li, Rong Guo, David Elashoff, Greg M. Cole, and et al. 2022. "Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue" International Journal of Molecular Sciences 23, no. 9: 5257. https://doi.org/10.3390/ijms23095257