Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection
Abstract
:1. Introduction
2. Results
2.1. The Metabolomics Dataset in Dogs Infected with B. canis
2.2. Untargeted LC-MS Metabolomics Analysis
2.3. Targeted LC-MS Metabolomics Analysis (Biocrates Analysis)
2.4. GC-MS Metabolomics Analysis
2.5. Principal Component Analysis
2.6. Hierarchical Clustering Analysis
2.7. Discriminant Metabolite Identification
2.8. Pathway Analysis and Enrichment Analysis
3. Discussion
4. Materials and Methods
4.1. Ethics Statement
4.2. Experimental Design
4.3. Blood Sample Preparation and Analysis
4.4. Untargeted LC-MS Metabolomics Analysis
4.5. Targeted LC-MS Metabolomics Analysis
4.6. GC-MS Metabolomics Analysis
4.7. Statistical Analyses
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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Metabolite | Peak ID | Mass | RT(s) | p-Value | Log2 (FC) |
---|---|---|---|---|---|
Inosine | 1280 | 267.0736 | 591.68 | 1.74 × 10−10 | 4.62 |
Hypoxanthine | 70 | 137.0458 | 567.72 | 3.00 × 10−6 | 2.95 |
Choline phosphate | 352 | 184.0734 | 714.56 | 8.90 × 10−5 | 2.29 |
Imidazole-4-acetate | 169 | 127.0502 | 624.14 | 6.69 × 10−4 | 1.81 |
Cystine | 407 | 241.031 | 771.48 | 1.59 × 10−4 | 1.54 |
Citrate | 848 | 191.02 | 828.92 | 5.74 × 10−4 | 0.95 |
Citrulline | 73 | 176.103 | 764.51 | 1.94 × 10−5 | 0.91 |
Methionine | 51 | 150.0584 | 610.06 | 1.50 × 10-4 | 0.76 |
Glycerol-3-phosphate | 1657 | 171.0066 | 713.52 | 3.26 × 10−3 | 0.62 |
Proline | 1004 | 114.0561 | 659.98 | 2.94 × 10−3 | 0.58 |
Pyroglutamic acid | 951 | 128.0354 | 575.74 | 3.86 × 10−4 | −0.70 |
Phenylalanine | 54 | 166.0863 | 551.14 | 9.88 × 10−7 | −1.13 |
Pyruvate | 1209 | 87.0088 | 501.48 | 3.05 × 10−5 | −1.15 |
Kynurenine | 199 | 209.0921 | 580.41 | 5.04 × 10−9 | −1.72 |
Metabolites | Short Name | p-Value | Log2 (FC) | Classification |
---|---|---|---|---|
Serotonin | Serotonin | 1.14 × 10−6 | 2.59 | Biogenic amines |
Methionine sulfoxide | Met-SO | 1.39 × 10−4 | 1.79 | Biogenic amines |
Citrulline | Cit | 2.50 × 10−6 | 1.01 | Amino acids |
Proline | Pro | 2.34 × 10−3 | 0.78 | Amino acids |
Methionine | Met | 5.87 × 10−3 | 0.70 | Amino acids |
Glycine | Gly | 1.45 × 10−2 | 0.42 | Amino acids |
Aspartic acid | Asp | 4.02 × 10−3 | −0.83 | Amino acids |
Phenylalanine | Phe | 2.32 × 10−6 | −1.06 | Amino acids |
Putrescine | Putrescine | 2.09 × 10−4 | −1.22 | Biogenic amines |
Kynurenine | Kynurenine | 7.76 × 10−8 | −1.59 | Biogenic amines |
Metabolite | Short Name | HMDB ID | Chemical Class |
---|---|---|---|
Lactic acid | Lac | 00190 | Organic acid |
Alanine | Ala | 00161 | Amino acid |
Glycine | Gly | 00123 | Amino acid |
Pyruvic acid | Pyruvic acid | 00243 | Organic acid |
3-Hydroxybutyric acid | 3-Hydroxybutyric acid | 00011 | Organic acid |
Valine | Val | 00883 | Amino acid |
Urea | Ur | 00294 | Organic acid |
Glycerol | Glycerol | 00131 | Carbohydrate |
Phosphoric acid | Phosphoric acid | NA | Organic acid |
Isoleucine | Ile | 00172 | Amino acid |
Proline | Pro | 00162 | Amino acid |
Serine | Ser | 00187 | Amino acid |
Threonine | Thr | 00167 | Amino acid |
Methionine | Met | 00696 | Amino acid |
L-Proline | L-Pro | 00162 | Amino acid |
Glutamic acid | Glu | 00148 | Organic acid |
Phenylalanine | Phe | 00159 | Amino acid |
Isoleucyl-Glutamine | Isoleucyl-Glutamine | 28905 | Amino acid |
Citric acid | Citric acid | 00094 | Organic acid |
Glucose | Glc | 00122 | Carbohydrate |
Lysine | Lys | 00182 | Amino acid |
Tyrosine | Tyr | 00158 | Amino acid |
Galactose | Gal | 00143 | Carbohydrate |
Palmitic acid | Palmitic acid | 00220 | Fatty acid |
Myo-inositol | Myo-inositol | 00211 | Sugar alcohol |
Stearic acid | Stearic acid | 00827 | Fatty acid |
Metabolic Pathways | Significant Metabolites (Fold Change) | p-Value | Pathway Impact |
---|---|---|---|
Glutathione metabolism | 5-oxoproline (up) Glycine (down) Putrescine (up) | 0.0073447 | 0.10 |
Alanine, aspartate, and glutamate metabolism | Citrate (down) Aspartate (up) Pyruvate (up) | 0.0073447 | 0.22 |
Glyoxylate and dicarboxylate metabolism | Pyruvate (up) Glycine (down) Citrate (down) | 0.010697 | 0.14 |
Cysteine and methionine metabolism | Cystine (down) Methionine (down) pyruvate (up) | 0.011653 | 0.10 |
Arginine and proline metabolism | Proline (down) Putrescine (up) Pyruvate (up) | 0.017166 | 0.19 |
Arginine biosynthesis | Citrulline (down) Aspartate (up) | 0.017204 | 0.23 |
Citrate cycle | Pyruvate (up) Citrate (down) | 0.034034 | 0.14 |
Phenylalanine, tyrosine, and tryptophan biosynthesis | Phenylalanine (up) | 0.048184 | 0.50 |
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Rubić, I.; Burchmore, R.; Weidt, S.; Regnault, C.; Kuleš, J.; Barić Rafaj, R.; Mašek, T.; Horvatić, A.; Crnogaj, M.; Eckersall, P.D.; et al. Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection. Int. J. Mol. Sci. 2022, 23, 1575. https://doi.org/10.3390/ijms23031575
Rubić I, Burchmore R, Weidt S, Regnault C, Kuleš J, Barić Rafaj R, Mašek T, Horvatić A, Crnogaj M, Eckersall PD, et al. Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection. International Journal of Molecular Sciences. 2022; 23(3):1575. https://doi.org/10.3390/ijms23031575
Chicago/Turabian StyleRubić, Ivana, Richard Burchmore, Stefan Weidt, Clement Regnault, Josipa Kuleš, Renata Barić Rafaj, Tomislav Mašek, Anita Horvatić, Martina Crnogaj, Peter David Eckersall, and et al. 2022. "Multi Platforms Strategies and Metabolomics Approaches for the Investigation of Comprehensive Metabolite Profile in Dogs with Babesia canis Infection" International Journal of Molecular Sciences 23, no. 3: 1575. https://doi.org/10.3390/ijms23031575