Table 3.
The Model Accurately Identifies Sites of N-Dealkylationa
| isozyme | top-two
|
average N–C AUC
|
global N–C AUC
|
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| self | MT | ST | HR | self | MT | ST | HR | self | MT | ST | HR | |
| HLM | 98.9 | 96.6 | 95.7 | 80.8 | 96.1 | 93.7 | 92.9 | 81.4 | 97.5 | 95.6 | 95.4 | 87.1 |
| CYP1A2 | 98.9 | 96.6 | 94.9 | 86.5 | 97.0 | 95.0 | 91.5 | 87.2 | 95.1 | 90.1 | 90.5 | 83.4 |
| CYP2A6 | 100 | 98.7 | 98.7 | 88.4 | 96.2 | 94.8 | 86.4 | 80.9 | 96.3 | 88.2 | 87.7 | 84.4 |
| CYP2B6 | 99.1 | 99.1 | 96.3 | 90.2 | 99.7 | 98.9 | 94.4 | 89.9 | 97.3 | 92.4 | 90.8 | 87.1 |
| CYP2C19 | 100 | 98.6 | 95.9 | 86.3 | 98.7 | 97.3 | 96.4 | 91.4 | 97.0 | 92.8 | 92.3 | 84.8 |
| CYP2C8 | 100 | 97.8 | 96.8 | 85.4 | 98.3 | 96.4 | 93.9 | 88.2 | 95.4 | 89.3 | 88.6 | 82.9 |
| CYP2C9 | 99.2 | 97.5 | 95.8 | 88.7 | 98.4 | 97.4 | 96.5 | 93.4 | 96.3 | 90.6 | 89.9 | 85.8 |
| CYP2D6 | 100 | 99.0 | 98.5 | 89.6 | 98.2 | 97.0 | 97.0 | 91.9 | 95.7 | 91.4 | 90.7 | 84.4 |
| CYP2E1 | 98.1 | 97.2 | 96.3 | 84.8 | 95.8 | 93.9 | 89.6 | 81.2 | 96.7 | 91.6 | 89.4 | 83.9 |
| CYP3A4 | 98.2 | 96.1 | 96.6 | 80.1 | 98.2 | 95.8 | 95.5 | 86.8 | 95.9 | 90.9 | 90.2 | 82.8 |
The table contains 10-fold cross-validated top-two, average N–C AUC, and global N–C AUC performance of the multitask (MT), single target (ST), and heuristic (HR) models. Accuracies of the MT model on the training data set (self) are also included for reference. For each metric, the highest cross-validated performance is bolded. Any scores not statistically different from the best performance are italicized. In all cases, the neural networks are significantly better than the heuristic model. The performance difference between the HLM single target and the multitask models by top-two and average N–C AUC is not significant (P = 0.352 and 0.425, respectively, by Mann–Wittney U test). The performance difference by global N–C AUC is statistically significant (P = 0.021 by paired permutation test).