TABLE III.
Test Set Chemicals, N = 40
| 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 ML + GEF MoA Calls | |||||||
| RF | LR | ANN | RF | LR | ANN | |||||||||||
| 10j | Test | Aneugen | – | + | + | – | – | – | + | A | + | – | + | A | + | A |
| 13m | Test | Aneugen | – | – | + | – | – | + | – | – | – | – | – | |||
| 14n | Test | Aneugen | – | – | – | – | – | – | – | – | – | – | – | |||
| 17q | Test | Aneugen | + | + | + | – | – | – | + | A | + | – | + | A | + | A |
| 6f | Test | Aneugen | – | – | – | – | – | + | – | – | – | – | – | |||
| Hesperadin | Test | Aneugen | – | + | + | – | + | – | + | A | + | – | + | A | + | A |
| Tozasertib | Test | Aneugen | – | + | + | – | – | – | + | A | + | – | + | A | + | A |
| ZM-447439 | Test | Aneugen | – | + | + | – | – | – | + | A | + | – | + | A | + | A |
| 3c | Test | Aneugen, possibly >1 MoA | + | + | + | – | – | + | + | A | + | – | + | A | + | A |
| 16p | Test | Aneugen, likely >1 MoA | + | + | + | – | + | + | + | A / C | + | – | + | A / C | + | A / C |
| 1a | Test | Genotoxic, likely > 1 MoA | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| 7g | Test | Genotoxic, MoA uncertain | – | – | – | + | + | – | + | C | – | – | – | + | C | |
| 9i | Test | Clastogen | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| Beta-Lapachone | Test | Clastogen | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| Ciprofloxacin | Test | Clastogen | – | + | + | – | – | – | + | A | – | – | – | + | A | |
| Dasatinib | Test | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Genistein | Test | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Irinotecan | Test | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| Mitoxantrone | Test | Clastogen | – | – | + | + | + | + | + | C | – | + | + | C | + | C |
| Teniposide | Test | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| 19s | Test | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| 20t | Test | Clastogen | – | – | – | – | + | + | + | C | – | – | – | + | C | |
| 4d | Test | Clastogen | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| 6-Thioguanine | Test | Clastogen | – | – | – | – | + | + | + | C | – | + | + | C | + | C |
| AZD2858 | Test | Clastogen, possibly >1 MoA | – | – | – | + | – | + | + | C | – | – | – | + | C | |
| 11k | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| 12l | Test | Non-genotoxicant | – | – | – | + | + | + | + | C | – | + | + | C | + | C |
| 15o | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| 18r | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| 2b | Test | Non-genotoxicant | – | – | – | + | + | + | + | C | – | – | – | + | C | |
| 5e | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| 8h | Test | Non-genotoxicant | – | – | – | – | – | + | – | – | – | – | – | – | ||
| Ampicillin | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| Anisomycin | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| Chlorocholine | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| Menthol | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| Osmertinib | Test | Non-genotoxicant | – | – | – | + | – | – | – | – | – | – | – | – | ||
| Topiramate | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| Tris (2-ethylhexyl) phosphate | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| Zafirlukast | Test | Non-genotoxicant | – | – | – | – | – | – | – | – | – | – | – | – | ||
| Concordance with a priori Expectation, Test Set: | 35/40 | 21/24 | 30/40 | 15/17 | 35/40 | 21/24 | ||||||||||
| 88% | 88% | 75% | 88% | 88% | 88% | |||||||||||
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.