Table 2:
The description of various feature spaces used in this study.
| Feature Space | Dimensions after feature selection (where applicable) | Description | Signal Expected | Source |
|---|---|---|---|---|
| Chemical Structure | 2048-bit vector | ECFP4 (Morgan) fingerprints representing chemical structures | Distinctive patterns of chemical bonding and arrangement | 52 |
| Physicochemical properties (Mordred Descriptors) | 1038 2-D descriptors | Properties such as lipophilicity, solubility, molecular weight, ionizing potential, etc. | Properties that are associated with negative impacts on ion channels in the heart | 41 |
| MOA dataset | 264 binary encoded MOAs + 551 known targets | Annotations for mechanism of action and known targets based on knowledge. | Mechanism of action for drugs that inhibit certain ion channels | 29 |
| CellScape Target Prediction dataset | 1893 predictions for 817 unique targets and concentration combinations (0.1, 1, 10, and 100uM) | Predicted protein target for inhibition/antagonism; does not consider the functionality; prediction is based on chemical structure; updated algorithm from PIDGINv443 | Understanding how a drug interacts with various biological targets (not just its primary target) can provide insights into potential off-target effects | 34,43 |
| Cell Painting | 1783 features | Morphological changes in U2OS cells by a chemical perturbation, using a 5-channel fluorescence microscopy assay | Morphological changes in cells that reflect basic biological processes | 24,53 |
| Gene Expression | 978 features | Transcriptomic changes in response to chemicals using the L1000 assay | Upregulation or downregulation of genes associated with cardiac stress, apoptosis in cardiac cells, or ion channel function | 19,25 |
| Gene Ontology | 4438 annotations | Gene Ontology manual annotations based on collective knowledge | Understanding the biological processes, cellular components, and molecular functions affected, e.g., related to cardiac function, cardiac muscle tissue development, or ion homeostasis | 19,26 |
| Cmax | 2 features | The maximum total and unbound concentration of a drug in plasma | High Cmax would indicate a high risk of cardiotoxicity | 30 |