TABLE II.
Training Set Chemicals, N = 85
| Chemical | Group | a priori Genotox Expectation | Machine Learning (ML) Ensemble | Global Evaluation Factor (GEF) Rubric | ML + GEF | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Aneugen Calls | Clastogen Calls | Overall ML Genotoxicity Call | Overall ML MoA Call | Aneugen Calls | Clastogen Calls | Overall GEF Genotoxicity Calls | Overall GEF MoA Calls | Overall ML + GEF Genotoxicity Calls | Overall MF + GEF MoA Calls | |||||||
| RF | LR | ANN | RF | FR | ANN | |||||||||||
| 17B-Estradiol | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| AMG-900 | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Carbendazim | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Colchicine | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Crizotinib | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Diethylstilbestrol | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Flubendazole | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Griseofulvin | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Mebendazole | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Nocodazole | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Noscapine | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Paclitaxel | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Vinblastine sulfate | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| Vincristine sulfate | Training | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| 1,3-Propane sultone | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| 4-Nitroquinoline N-oxide | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| 5-Fluorouracil | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Aphidicolin | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Azathioprine | Training | Clastogen | – | – | – | + | – | + | + | C | – | – | – | + | C | |
| Azidothymidine | Training | Clastogen | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| Bleomycin sulfate | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Camptothecin | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Chlorambucil | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Cisplatin | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Cytosine Arabinoside | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Doxorubicin | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Emodin | Training | Clastogen | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| Ethyl methanesulfonate | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Etoposide | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Glycidamide | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Hydralazine | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Hydrogen peroxide | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Hydroxyurea | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Melphalan | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Menadione | Training | Clastogen | – | – | – | + | + | – | + | C | – | – | – | + | C | |
| Methotrexate | Training | Clastogen | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| Methyl methanesulfonate | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Mitomycin C | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| N-Ethyl-N-nitrosourea | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| N-Methyl-N’-nitro-N-nitrosoguanidine | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Olaparib | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Propyl gallate | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Resorcinol diglycidyl ether | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Stavudine | Training | Clastogen | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| Temozolomide | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Thiotepa | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Topotecan | Training | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Alosetron | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Amitrole | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Anthranillic acid | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Brefeldin A | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Caffeine | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| CCCP | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Clofibrate | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Cyclohexanone | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Cycloheximide | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| D-Limonene | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| D-Mannitol | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Dexamethasone | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Dextrose | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Di-(2-ethylhexyl) phthalate | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Diethanolamine | Training | Non-genotoxicant | – | – | – | – | – | + | – | – | – | – | – | |||
| Erythromycin | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Famotidine | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Imatinib mesylate | Training | Non-genotoxicant | – | – | – | – | + | + | + | C | – | – | – | + | C | |
| Hexachloroethane | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Lidocaine | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Lovastatin | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Melamine | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Methyl carbamate | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| N-Butyl chloride | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Ofloxacin | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Paroxetine | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Phenanthrene | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Phenformin HCl | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Progesterone | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Pyridine | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Sodium chloride | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Sodium dodecyl sulfate | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Sucrose | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Tert-butyl alcohol | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Thapsigargin | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Tolterodine l-tartrate | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Tunicamycin | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Zonisamide | Training | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | |||
| Concordance with a priori Expectation, Training Set: | 84/85 | 47/48 | 79/85 | 41/41 | 84/85 | 47/48 | ||||||||||
| 99% | 98% | 93% | 100% | 99% | 98% | |||||||||||
Column 3 is color coded as to “a priori Genotox Expectation”, where aneugen = blue, clastogen = yellow, non-genotoxicant = white, and likely ≥ 1 MoA = green.
Columns 4+ are color coded as to Machine Learning and Global Evaluation Factor predictions, where aneugen = blue, clastogen = yellow, non-genotoxicant = white, and likely ≥ 1 MoA = green.