| --- |
| license: cc-by-4.0 |
| language: |
| - en |
| task_categories: |
| - tabular-regression |
| - tabular-classification |
| tags: |
| - chemistry |
| - drug-discovery |
| - cardiotoxicity |
| - hERG |
| - Nav1.5 |
| - Cav1.2 |
| - IKs |
| - ion-channels |
| - QSAR |
| - ChEMBL |
| - cipa |
| - benchmark |
| pretty_name: CardioSafe ion-channel benchmark |
| size_categories: |
| - 100K<n<1M |
| configs: |
| - config_name: tan70_v1_0 |
| data_files: |
| - split: train |
| path: tan70_v1_0/train.parquet |
| - split: validation |
| path: tan70_v1_0/validation.parquet |
| - split: test |
| path: tan70_v1_0/test.parquet |
| - config_name: tan60_v1_0 |
| data_files: |
| - split: train |
| path: tan60_v1_0/train.parquet |
| - split: validation |
| path: tan60_v1_0/validation.parquet |
| - split: test |
| path: tan60_v1_0/test.parquet |
| - config_name: tan70_v1_1 |
| data_files: |
| - split: train |
| path: tan70_v1_1/train.parquet |
| - split: validation |
| path: tan70_v1_1/validation.parquet |
| - split: test |
| path: tan70_v1_1/test.parquet |
| - config_name: tan60_v1_1 |
| data_files: |
| - split: train |
| path: tan60_v1_1/train.parquet |
| - split: validation |
| path: tan60_v1_1/validation.parquet |
| - split: test |
| path: tan60_v1_1/test.parquet |
| --- |
| |
| # CardioSafe ion-channel benchmark |
|
|
| Curated multi-task ion-channel labels + Tanimoto-controlled splits + |
| supplementary materials for **CardioSafe: multi-task prediction of |
| cardiac ion channel activity with reverse-leak audited benchmarking** |
| (Jovanović et al., 2026, |
| [bioRxiv](https://www.biorxiv.org/content/10.64898/2026.05.06.723181v1)). |
|
|
| The canonical source is the |
| [CardioSafe-benchmark GitHub repository](https://github.com/AppliedScientific/CardioSafe-benchmark). |
| This HF Datasets repo mirrors `data/` from that deposit and adds |
| pre-joined per-fold Parquet shards so you can write: |
|
|
| ```python |
| from datasets import load_dataset |
| |
| # v1.1 (audit-clean) test fold on the tan70 Tanimoto cutoff: |
| ds = load_dataset("appliedscientific/cardiosafe-benchmark", |
| "tan70_v1_1", split="test") |
| print(ds.column_names) |
| # ['row_idx', 'smiles', 'inchikey', 'herg_pchembl', 'herg_blocker_10um', |
| # 'herg_blocker_1um', 'nav15_pchembl', 'nav15_blocker', 'cav12_pchembl', |
| # 'cav12_blocker', 'iks_blocker'] |
| ``` |
|
|
| Each row is one curated compound. Label columns are NaN-sparse — only |
| those compounds with primary-screen evidence for the relevant channel |
| have non-null values. |
|
|
| ## Configs (pre-joined splits) |
|
|
| | Config | Split strategy | Version | Compounds (train / val / test) | |
| | --- | --- | --- | --- | |
| | `tan70_v1_0` | Tanimoto ≥ 0.70 cutoff | v1.0 preprint | 241,792 / 46,326 / 46,326 | |
| | `tan60_v1_0` | Tanimoto ≥ 0.60 cutoff | v1.0 preprint | 306,665 / 13,889 / 13,889 | |
| | `tan70_v1_1` | Tanimoto ≥ 0.70 cutoff | v1.1 retrain | 241,790 / 46,328 / 46,326 | |
| | `tan60_v1_1` | Tanimoto ≥ 0.60 cutoff | v1.1 retrain | 306,662 / 13,892 / 13,889 | |
|
|
| **v1.1 differs from v1.0 by 2 force-routed analogs in the cardiac-cliff |
| cluster** (terfenadine/fexofenadine/HMT). The test fold is identical |
| across v1.0 and v1.1 — paper Table 2/3 metrics are unchanged. See |
| [`supplementary/note_s3_v1_1_audit_correction.md`](https://github.com/AppliedScientific/CardioSafe-benchmark/blob/main/data/supplementary/note_s3_v1_1_audit_correction.md). |
|
|
| ## Label schema |
|
|
| | Column | Head | Type | |
| | --- | --- | --- | |
| | `herg_pchembl` | regression — hERG pIC50 | float | |
| | `herg_blocker_10um` | hERG blocker @ 10 µM | binary {0, 1} | |
| | `herg_blocker_1um` | hERG blocker @ 1 µM | binary {0, 1} | |
| | `nav15_pchembl` | regression — Nav1.5 pIC50 | float | |
| | `nav15_blocker` | Nav1.5 blocker @ 10 µM | binary {0, 1} | |
| | `cav12_pchembl` | regression — Cav1.2 pIC50 | float | |
| | `cav12_blocker` | Cav1.2 blocker @ 10 µM | binary {0, 1} | |
| | `iks_blocker` | IKs blocker @ 10 µM (exploratory) | binary {0, 1} | |
|
|
| IKs has no regression head (n = 115 labelled compounds; treated as |
| exploratory). |
|
|
| Per-channel label counts (primary binary head, all folds combined): |
|
|
| | Channel | n labelled | n blockers | |
| | --- | --- | --- | |
| | hERG (10 µM) | 331,127 | 11,881 | |
| | Nav1.5 (10 µM) | 3,160 | 1,240 | |
| | Cav1.2 (10 µM) | 1,138 | 548 | |
| | IKs (10 µM) | 115 | 30 | |
|
|
| ## Raw canonical files |
|
|
| `raw/` contains the source-of-truth files exactly as published in the |
| GitHub repo, for power users doing custom merges: |
|
|
| ``` |
| raw/ |
| ├── compounds.parquet # 334,444 × (row_idx, smiles, inchikey) |
| ├── labels.parquet # 334,444 × 8 sparse labels |
| ├── splits/ |
| │ ├── tan70.parquet # v1.0 — paper preprint splits |
| │ ├── tan60.parquet |
| │ ├── tan70_v1_1.parquet # v1.1 — audit-clean retrain splits |
| │ └── tan60_v1_1.parquet |
| ├── labels_MANIFEST.json # curation provenance (sources, voting policy) |
| ├── splits_CHANGELOG.md # v1.0 → v1.1 diff |
| └── README.md # full data-deposit notes from GitHub |
| ``` |
|
|
| All splits share the same `row_idx` keying — join on it for arbitrary |
| slicing. |
|
|
| ## Comparators |
|
|
| `comparators/` ships the CToxPred2 and CardioGenAI predictions on the |
| v1.0 `tan70` test fold, the inputs to the reverse-leak audit and the |
| head-to-head comparison in paper Tables 3 / 3b / S2 / S3 / Figure 4. |
|
|
| ## Supplementary materials |
|
|
| `supplementary/` ships verbatim: |
| - **Notes S1, S2, S3** — Y-randomization mechanism; activity-cliff |
| curation provenance + bibliography + per-pair composition + filtered |
| cliff manifests; audit-driven v1.1 correction + retrain metrics + the |
| cardiac-cliff case study |
| - **Tables S0, S1, S2, S3, S5, S6, S7, S8, S9** — descriptor spec, |
| per-head confusion matrices, comparator panels pre/post de-leak, tan60 |
| drug panel, failure-mode SMILES, AD per-bin metrics, L1000 threshold |
| sweep, curation sensitivity (no S4 — paper supplementary numbering |
| jumps S3 → S5) |
| - **Figure S1** — hERG reliability curves across applicability-domain |
| bins (PDF + PNG + JSON of the underlying decile data) |
|
|
| ## Source data |
|
|
| - **Labels** are derived from ChEMBL 36 (source dump SHA-256 |
| `b25820eef0f0481ad7712bdf4bac3b45f354e3cbacb76be1fdbf4205d6b48fb9`, |
| available from <https://www.ebi.ac.uk/chembl/>) and the **hERG Central |
| primary screen**, under a pharmacology-aware curation policy that |
| retains censored values and inhibition-percentage votes. Full |
| provenance lives in `raw/labels_MANIFEST.json`. |
| - **Splits** are Tanimoto-controlled across train / val / test on |
| Morgan-r2-2048 fingerprints, with terfenadine and fexofenadine |
| force-routed to `val` so the canonical cardiac activity cliff is |
| available as a held-out case study. v1.1 additionally force-routes the |
| hydroxymethyl-terfenadine analogs flagged by an exhaustive |
| O(n_train × n_other) Tanimoto leakage audit |
| (`scripts/audit_tanimoto_leak.py` in the GitHub repo). |
|
|
| ## What is **not** here |
|
|
| - **L1000 raw signatures** used to train the expression encoder — |
| available from GEO under GSE92742 (Phase I) and GSE70138 (Phase II). |
| - **Continually-updated production ensemble** — served at |
| [platform.appliedscientific.ai/cardiosafe](https://platform.appliedscientific.ai/cardiosafe). |
| This deposit is the frozen paper snapshot. |
| - **Model weights** — at |
| [`appliedscientific/cardiosafe`](https://huggingface.co/appliedscientific/cardiosafe) |
| (5-seed v1.0 + v1.1 ensembles + L1000 encoder, CC-BY-NC-4.0). |
| - **Interactive demo** — at |
| [`appliedscientific/cardiosafe` (Space)](https://huggingface.co/spaces/appliedscientific/cardiosafe). |
|
|
| ## License |
|
|
| CC-BY-4.0. Use with attribution; commercial use allowed under the |
| license terms. See the |
| [full LICENSE-DATA](https://github.com/AppliedScientific/CardioSafe-benchmark/blob/main/LICENSE-DATA) |
| in the GitHub repo for the exact text. |
|
|
| Note: the *model weights* are CC-BY-NC-4.0 (non-commercial), not the |
| data. They live at a separate HF repo — |
| [`appliedscientific/cardiosafe`](https://huggingface.co/appliedscientific/cardiosafe). |
|
|
| ## Citation |
|
|
| ```bibtex |
| @article{cardiosafe2026, |
| title = {CardioSafe: multi-task prediction of cardiac ion channel |
| activity with reverse-leak audited benchmarking}, |
| author = {Jovanović, Mihailo and Weidener, Lukas and Brkić, Marko and |
| Ulgac, Emre and Meduri, Aakaash}, |
| year = {2026}, |
| journal = {bioRxiv}, |
| doi = {10.64898/2026.05.06.723181}, |
| url = {https://www.biorxiv.org/content/10.64898/2026.05.06.723181v1} |
| } |
| ``` |
|
|
