Identification of Biomarkers for Methamphetamine Exposure Time Prediction in Mice Using Metabolomics and Machine Learning Approaches
Abstract
:1. Introduction
2. Experimental Design
2.1. Regents
2.2. Instruments
2.3. Animal and Sample Preparation
2.4. Sample Preparation for GC/MS Analysis and Compound Identification
2.5. Machine Learning Methods for the Prediction of Drug Exposure Time
2.6. Statistical Analysis
3. Results
3.1. Endogenous Metabolite Identification
3.2. Multivariate and Univariate Data Analysis
3.3. Machine Learning Method Selection and Optimization
3.4. Metabolic Pathway Analysis
3.5. Biomarker Selection and Random Forest Model Optimization to Predict Drug Exposure Time
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Metabolic Pathways | Compounds | Serum | Urine | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Methamphetamine Treatment | Withdrawal | Relapse | Methamphetamine Treatment | Withdrawal | Relapse | ||||||
10DvsC | 15DvsC | 20DvsC | Wvs15D | Rvs20D | 10DvsC | 15DvsC | 20DvsC | Wvs15D | Rvs20D | ||
Lipid metabolism | Lauric acid | ↓ * | ↓ | ↓ * | ↑ * | - | — | — | — | — | — |
Myristic acid | ↓ * | ↓ * | ↓ * | ↑ * | - | — | — | — | — | — | |
Oleic acid | ↓ * | ↓ * | ↓ * | ↑ * | - | — | — | — | — | — | |
Palmitic acid | ↓ * | ↓ * | ↓ * | ↑ * | - | ↓ | - | ↑ | - | - | |
Octadecanoic acid | ↓ | ↓ * | ↓ * | ↑ * | ↑ | ↓ * | ↓ | ↓ | ↑ | ↑ * | |
Cis-9-hexadecenoic acid | ↓ * | ↓ * | ↓ * | ↑ * | - | — | — | — | — | — | |
Arachidonic acid | ↓ | ↓ * | ↓ * | ↑ * | ↑ | - | ↑ | ↑ | - | - | |
Monopalmitin | ↓ * | ↓ * | ↓ * | ↑ * | ↑ * | — | — | — | — | — | |
1-Monostearin | ↓ * | ↓ * | ↓ * | ↑ * | ↑ * | — | — | — | — | — | |
Cholesterol-TMS | ↑ | ↑ | ↑ * | ↓ | ↑ | — | — | — | — | — | |
Glycerol-3TMS | ↓ * | ↓ * | ↓ * | - | - | — | — | — | — | — | |
cis-4,7,10,13,16,19-docosahexaenoic acid | ↓ * | ↓ * | ↓ * | - | - | — | — | — | — | — | |
Carbohydrate metabolism | Pyruvate | ↓ * | ↓ * | - | ↑ * | ↓ | ↓ | ↑ | ↑ | - | ↓ |
Lactate | ↓ | ↓ * | - | - | - | ↑ | ↑ | ↑ | - | ↓ | |
Myo-Inositol | ↓ | ↓ * | - | ↑ | ↓ | ↑ | ↑ | ↑ * | ↓ | ↓ | |
Glyceric acid | ↓ | ↓ | ↓ * | ↑ * | - | - | ↓ | ↑ | - | ↑ | |
Glucose-6-phosphate | ↓ * | ↑ | ↓ | ↓ * | ↓ | — | — | — | — | — | |
Glycerol-3-phosphate | ↓ * | ↓ * | ↓ * | ↑ * | - | — | — | — | — | — | |
3-Hydroxybutyric acid | ↓ | ↓ | - | - | ↑ | ↑ | ↑ | ↑ | ↓ | ↑ * | |
Glucose | - | - | ↓ | - | ↓ | - | ↑ | - | ↓ | - | |
Fructose | ↓ * | ↓ * | ↓ * | ↑ * | - | - | ↑ * | - | ↓ | ↓ | |
TCA cycle | Succinate | ↓ | ↓ | ↑ | ↑ | ↑ | ↓ * | ↓ | ↓ * | ↑ | ↓ |
Fumarate | ↓ * | ↓ * | - | - | - | ↓ | - | ↓ | - | - | |
Malate-3TMS | ↓ * | ↓ * | ↓ | ↑ * | - | ↓ | - | ↓ | ↓ | ↓ | |
Citrate | ↓ | ↓ | - | ↑ | - | ↓ * | ↓ * | - | ↑ | ↓ | |
2-Ketoglutaric acid | ↑ | ↑ | ↓ | ↑ | ↑ * | ↓ * | ↓ | ↓ * | ↑ | ↓ | |
Glutamate-3TMS | ↓ * | ↓ * | ↓ * | ↑ * | - | ↓ | - | ↓ | ↓ | ↓ | |
Glutamine-3TMS | ↑ * | ↑ * | ↑ * | ↓ | ↓ * | ↑ | ↑ | ↑ * | ↓ | ↑ | |
Amino acid metabolism | Aspartate-2TMS | ↓ * | ↓ * | ↓ * | ↑ * | - | — | — | — | — | — |
Asparagine | ↑ * | ↑ * | ↑ * | ↑ | ↓ | — | — | — | — | — | |
Alanine | ↑ * | ↑ * | ↑ * | - | - | ↓ | ↑ | ↑ | ↓ | ↓ | |
Leucine | ↑ * | ↑ * | ↑ * | - | - | — | — | — | — | — | |
Isoleucine | ↑ * | ↑ * | ↑ * | - | - | — | — | — | — | — | |
Valine | ↑ * | ↑ * | ↑ * | - | ↓ | — | — | — | — | — | |
5-Hydroxytryptamine | ↓ * | ↓ * | ↓ * | ↑ * | - | — | — | — | — | — | |
Phenylalanine | ↑ * | ↑ * | ↑ * | - | - | — | — | — | — | — | |
Lysine | ↑ * | ↑ * | ↑ * | - | ↓ | ↓ | ↓ | - | - | ↓ | |
Proline | ↑ * | ↑ * | ↑ * | ↑ | ↓ | ↓ | ↓ | - | - | ↑ | |
Glutathione metabolism | Serine-3TMS | ↑ * | ↑ * | ↑ * | - | ↓ | ↑ | ↑ | ↑ * | ↓ | ↓ |
Cysteine | - | - | - | - | - | ↓ | ↓ | - | ↑ * | - | |
Glycine-TMS | - | ↑ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | - | ↓ | |
Methionine | ↑ * | ↑ * | ↑ * | ↑ * | - | - | ↑ | ↑ | ↓ | ↓ | |
Purine metabolism | Hypoxanthine | ↑ | ↑ | ↑ | - | ↓ | ↑ * | ↑ * | ↑ | ↓ * | ↓ * |
Xanthine | ↑ | ↑ | ↑ | - | ↓ | ↑ | ↑ | ↑ * | ↓ | ↓ * | |
Uric acid | ↑ | ↑ | ↓ | ↓ | ↑ * | ↑ | ↑ | ↑ * | ↓ | ↓ * | |
Ornithine | ↑ * | ↑ | ↑ * | ↑ * | ↓ | ↓ * | ↓ * | - | ↑ * | ↑ | |
Others | Aminomalonic acid | ↑ * | ↑ | ↑ | ↑ | ↓ | — | — | — | — | — |
Oxalic acid | ↑ | - | ↑ | - | - | ↑ | ↑ * | ↑ * | ↓ | ↓ | |
Phosphate | ↓ * | ↓ * | ↓ * | - | - | ↓ * | ↓ | - | ↑ | ↑ | |
Glutaric acid | — | — | — | — | — | ↑ * | ↑ * | ↑ * | ↑ | ↓ | |
N-Acetylaspartate-2TMS | — | — | — | — | — | - | ↑ | ↑ * | - | ↓ | |
3-Hydroxyisobutyric acid | — | — | — | — | — | ↑ | ↑ | ↑ | ↓ | - | |
γ-Aminobutyric acid | — | — | — | — | — | ↓ | ↓ | - | ↑ | ↓ | |
Niacinamide | — | — | — | — | — | ↓ | ↑ | ↑ * | ↓ | ↓ | |
Hippuric acid | — | — | — | — | — | - | ↑ * | ↑ | ↓ | ↓ * | |
2-Hydroxyglutaric acid (3TMS) | — | — | — | — | — | - | ↑ | - | ↑ | ↑ |
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Sheng, W.; Sun, R.; Zhang, R.; Xu, P.; Wang, Y.; Xu, H.; Aa, J.; Wang, G.; Xie, Y. Identification of Biomarkers for Methamphetamine Exposure Time Prediction in Mice Using Metabolomics and Machine Learning Approaches. Metabolites 2022, 12, 1250. https://doi.org/10.3390/metabo12121250
Sheng W, Sun R, Zhang R, Xu P, Wang Y, Xu H, Aa J, Wang G, Xie Y. Identification of Biomarkers for Methamphetamine Exposure Time Prediction in Mice Using Metabolomics and Machine Learning Approaches. Metabolites. 2022; 12(12):1250. https://doi.org/10.3390/metabo12121250
Chicago/Turabian StyleSheng, Wei, Runbin Sun, Ran Zhang, Peng Xu, Youmei Wang, Hui Xu, Jiye Aa, Guangji Wang, and Yuan Xie. 2022. "Identification of Biomarkers for Methamphetamine Exposure Time Prediction in Mice Using Metabolomics and Machine Learning Approaches" Metabolites 12, no. 12: 1250. https://doi.org/10.3390/metabo12121250
APA StyleSheng, W., Sun, R., Zhang, R., Xu, P., Wang, Y., Xu, H., Aa, J., Wang, G., & Xie, Y. (2022). Identification of Biomarkers for Methamphetamine Exposure Time Prediction in Mice Using Metabolomics and Machine Learning Approaches. Metabolites, 12(12), 1250. https://doi.org/10.3390/metabo12121250