Table 2.
Performance of selected metabolites at each time period as assessed by ROC analysis.
| Time Range | Metabolites | AUC | p-Value (t-Test) | Cut-Off Value |
|---|---|---|---|---|
| All times | 1R,6R-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate | 1 | 2.0454 × 10−21 | 5 |
| Hydroxyhydrocinnamic acid | 1 | 5.7497 × 10−28 | 2.64 | |
| multiplex pred | 1 | 6.8817 × 10−57 | 0.665 | |
| 3,4-dihydroxyphenylacetate | 0.99593 | 1.35 × 10−14 | 0.63 | |
| 3(7-dehydro)genipinic acid | 0.98008 | 7.1576 × 10−14 | 4.3 | |
| Nonate | 0.97737 | 3.9231 × 10−17 | 2.47 | |
| 12-demethylated-8-hydroxygenipinic acid | 0.95292 | 5.7703 × 10−7 | 0.00878 | |
| Dihydroxyhydrocinnamic acid | 0.93074 | 3.0562 × 10−18 | 37.8 | |
| Genipic acid | 0.85785 | 1.0072 × 10−9 | 0.322 | |
| Genipic acid glucuronide | 0.74423 | 0.55998 | 0.218 | |
| 0 to 6 h | Dihydroxyhydrocinnamic acid | 1 | 1.9091 × 10−14 | 48.9 |
| 1R,6R-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate | 1 | 9.9186 × 10−10 | 3.95 | |
| Hydroxyhydrocinnamic acid | 1 | 7.7957 × 10−12 | 3.56 | |
| Nonate | 1 | 8.2316 × 10−9 | 5.85 | |
| 3,4-dihydroxyphenylacetate | 1 | 1.6602 × 10−7 | 0.244 | |
| multiplex pred | 1 | 1.3766 × 10−22 | 0.633 | |
| Genipic acid | 0.98333 | 7.4173 × 10−8 | 0.342 | |
| 3(7-dehydro)genipinic acid | 0.95 | 5.951 × 10−7 | 4.14 | |
| 12-demethylated-8-hydroxygenipinic acid | 0.9375 | 2.574 × 10−4 | 0.0159 | |
| Genipic acid glucuronide | 0.93333 | 2.0461 × 10−4 | 0.17 | |
| 6 to 12 h | 1R,6R-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate | 1 | 6.1416 × 10−9 | 4.83 |
| Hydroxyhydrocinnamic acid | 1 | 1.7482 × 10−9 | 2.64 | |
| 12-Demethylated-8-hydroxygenipinic acid | 1 | 6.9629 × 10−5 | 0.00947 | |
| Nonate | 1 | 9.5177 × 10−6 | 3.09 | |
| 3,4-dihydroxyphenylacetate | 1 | 1.1069 × 10−4 | 0.892 | |
| multiplex pred | 1 | 2.2156 × 10−21 | 0.486 | |
| 3(7-dehydro)genipinic acid | 0.97917 | 1.3988 × 10−5 | 3.5 | |
| Dihydroxyhydrocinnamic acid | 0.93333 | 3.7546 × 10−6 | 36.8 | |
| Genipic acid | 0.77083 | 0.0073173 | 0.322 | |
| Genipic acid glucuronide | 0.7625 | 0.92915 | 0.374 | |
| 12 to 24 h | 1R,6R-6-Hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate | 1 | 6.279 × 10−6 | 6.12 |
| Hydroxyhydrocinnamic acid | 1 | 2.1664 × 10−10 | 3.85 | |
| 3,4-dihydroxyphenylacetate | 1 | 9.8555 × 10−6 | 0.63 | |
| multiplex pred | 1 | 1.4956 × 10−16 | 0.665 | |
| 3(7-dehydro)genipinic acid | 0.99219 | 1.2466 × 10−5 | 1.74 | |
| 12-demethylated-8-hydroxygenipinic acid | 0.92929 | 0.002416 | 0.0106 | |
| Nonate | 0.92578 | 1.7992 × 10−5 | 7.13 | |
| Dihydroxyhydrocinnamic acid | 0.86528 | 1.8911 × 10−4 | 50 | |
| Genipic acid | 0.83984 | 8.338 × 10−4 | 0.318 | |
| Genipic acid glucuronide | 0.55469 | 0.22484 | 0.242 |
The multiplex biomarker was steady across each time range, more than any of its individual constituent (Figure S1, Venny plot). In addition, in order to assess if the multiplex biomarker predictive scores determined at a selected time range can be used any time over 24 h, we permuted the threshold of each ROC model to determine the impact on genipap consumers and non-consumers’ status determination. The prediction was perfect until 12 h and was only minimally affected in the range 12–24 h, with one misclassified individual (Figure S2).