Table 2.
Altered metabolites with an average VIP score greater than or equal to 1.0 from the PLS-DA comparing SPMS with RRMS patients. A positive log2 fold change (FC) SP-RR indicates an averaged increase in SPMS compared with RRMS patients and vice versa. Identities confirmed by m/z and elution time of the internal standards and by MS/MS fragmentation pattern (validation level 2). Identities confirmed by m/z and elution time of the internal standards (validation level 1). Coefficient of variation (CV) is reported for all altered metabolites in the QC samples.
| Metabolite | KEGG | VIP Mean (95% CI) | log2 FC SP-RR | p-Value | FDR | CV | Validation Level |
|---|---|---|---|---|---|---|---|
| Thymine | C00178 | 2.01 (1.95, 2.07) | 0.49 | 5.0 × 10−5 | 1.8 × 10-3 | 7.9% | 1 |
| Glutarylcarnitine | - | 1.84 (1.79, 1.90) | 0.48 | 2.4 × 10−4 | 4.4 × 10-3 | 9.3% | 2 |
| Biliverdin | C00500 | 1.78 (1.72, 1.83) | 0.90 | 1.6 × 10−3 | 0.011 | 24.7% | 1 |
| Pipecolate | C00408 | 1.77 (1.70, 1.83) | 0.56 | 1.9 × 10−3 | 0.011 | 7.5% | 1 |
| Uridine | C00299 | 1.76 (1.70, 1.82) | 0.33 | 9.4 × 10−4 | 0.011 | 7.4% | 2 |
| 4-Acetamidobutanoate | C02946 | 1.72 (1.67, 1.78) | 0.40 | 2.1 × 10−3 | 0.011 | 9.2% | 2 |
| Deoxyuridine | C00526 | 1.67 (1.62, 1.72) | −0.50 | 1.4 × 10−3 | 0.011 | 13.8% | 1 |
| Ethylmalonate | - | 1.63 (1.56, 1.70) | 0.46 | 9.7 × 10−3 | 0.030 | 7.1% | 2 |
| Valine | C00183 | 1.61 (1.56, 1.66) | 0.25 | 4.2 × 10−3 | 0.020 | 4.5% | 2 |
| O-Succinyl-homoserine | C01118 | 1.57 (1.52, 1.62) | 0.24 | 6.4 × 10−3 | 0.021 | 14.3% | 1 |
| Methionine | C00073 | 1.56 (1.51, 1.62) | 0.32 | 6.0 × 10−3 | 0.021 | 3.4% | 2 |
| Glutamine | C00064 | 1.51 (1.46, 1.56) | 0.31 | 6.3 × 10−3 | 0.021 | 22.3% | 2 |
| 3-Methoxytyrosine [M + H] | - | 1.38 (1.31, 1.45) | 0.80 | 0.075 | 0.088 | 6.8% | 2 |
| Phenylacetate | C07086 | 1.38 (1.32, 1.43) | 0.26 | 0.031 | 0.052 | 8.7% | 2 |
| N-Acetylleucine | C02710 | 1.37 (1.33, 1.42) | 0.24 | 0.016 | 0.038 | 5.8% | 1 |
| Phenylalanine | C00079 | 1.35 (1.30, 1.39) | 0.23 | 0.021 | 0.043 | 4.6% | 2 |
| 1-Methyladenosine | C02494 | 1.34 (1.28, 1.39) | 0.26 | 0.017 | 0.040 | 11.5% | 2 |
| Urate | C00366 | 1.25 (1.20, 1.31) | 0.44 | 0.013 | 0.037 | 8.6% | 2 |
| Caffeine * | C07481 | 1.25 (1.18, 1.32) | −1.12 | 0.078 | 0.088 | 24.4% | 2 |
| Ketoleucine | C00233 | 1.25 (1.19, 1.31) | 0.09 | 0.034 | 0.052 | 7.6% | 2 |
| Tyrosine | C00082 | 1.25 (1.21, 1.29) | 0.25 | 0.034 | 0.052 | 5.2% | 2 |
| N6-(delta2-isopentenyl)-adenine | C04083 | 1.23 (1.17, 1.29) | 0.29 | 0.028 | 0.049 | 5.4% | 1 |
| N-Acetylphenylalanine * [M + H] | C03519 | 1.23 (1.18, 1.27) | 0.21 | 0.044 | 0.061 | 6.9% | 1 |
| 3-Methoxytyramine * | C05587 | 1.20 (1.14, 1.26) | −0.75 | 0.038 | 0.054 | 26.7% | 1 |
| Cyclic AMP | C00575 | 1.20 (1.10, 1.31) | 0.28 | 0.020 | 0.043 | 12.0% | 1 |
| N-Acetylserotonin | C00978 | 1.20 (1.15, 1.25) | 0.44 | 0.023 | 0.045 | 16.8% | 1 |
| 3,4-Dihydroxyphenylglycol | C05576 | 1.18 (1.13, 1.24) | 0.28 | 0.015 | 0.038 | 15.9% | 1 |
| Guanosine | C00387 | 1.17 (1.10, 1.25) | 0.16 | 0.035 | 0.052 | 7.8% | 2 |
| Kynurenine | C00328 | 1.12 (1.06, 1.18) | 0.37 | 0.048 | 0.063 | 7.9% | 2 |
| Isoleucine/Leucine | C00407 | 1.10 (1.05, 1.15) | 0.21 | 0.078 | 0.088 | 6.5% | 2 |
| Kynurenate | C01717 | 1.09 (1.02, 1.16) | 0.43 | 0.050 | 0.064 | 9.1% | 1 |
| 5-Hydroxytryptophan | C00643 | 1.09 (1.02, 1.15) | 0.45 | 0.055 | 0.068 | 15.8% | 1 |
| 3-Methoxytyrosine [M − H] | - | 1.08 (1.05, 1.12) | 0.65 | 0.146 | 0.150 | 12.0% | 1 |
| 4-Guanidinobutanoate | C01035 | 1.06 (1.01, 1.12) | −0.24 | 0.028 | 0.049 | 7.9% | 1 |
| 5-Hydroxyindoleacetate | C05635 | 1.06 (0.99, 1.12) | −0.35 | 0.083 | 0.091 | 11.7% | 1 |
| Trigonelline | C01004 | 1.05 (0.97, 1.12) | 0.09 | 0.157 | 0.157 | 11.3% | 1 |
| 3-Hydroxymethylglutarate | C03761 | 1.01 (0.94, 1.08) | −0.25 | 0.107 | 0.113 | 13.3% | 1 |
* Metabolite with a demonstrated age dependence that has been corrected. CI: confidence interval.