Update README.md

README.md

@@ -327,4 +327,229 @@ configs:
   data_files:
   - split: train
     path: multitask/train-*
+license: mit
+tags:
+- tabular
+pretty_name: TACK
 ---
+
+# TACK — TArgeting Chimeras Knowledge
+
+**A curated, ML-ready dataset and benchmark for PROTAC degradation activity prediction**
+
+[![Paper](https://img.shields.io/badge/Paper-KDD%202026-blue)](https://arxiv.org/abs/2605.19579)
+[![GitHub](https://img.shields.io/badge/Code-GitHub-black)](https://github.com/ribesstefano/TACK)
+[![Models](https://img.shields.io/badge/Models-Zenodo-green)](https://zenodo.org/uploads/15691822)
+[![License](https://img.shields.io/badge/License-MIT-yellow)](LICENSE)
+
+---
+
+## Overview
+
+Proteolysis-targeting chimeras (PROTACs) are a promising drug modality that induces targeted protein degradation by hijacking the cell's native ubiquitin–proteasome system. However, rational PROTAC design remains challenging due to the complex interplay between molecular structure, target proteins (POIs), E3 ligases, and cellular context.
+
+**TACK** addresses three critical gaps in existing PROTAC ML benchmarks:
+
+- **Data scarcity and inconsistency** — harmonized from three major public repositories with standardized SMILES, protein annotations, and experimental conditions
+- **Lack of rigorous benchmarks** — scaffold-based 5×5 cross-validation and formal statistical testing (Friedman, Wilcoxon, Tukey HSD) rather than simple train/test splits
+- **Limited scope** — supports regression (*pDC₅₀*, *D*max) and binary classification, not just the binary classification framing common in prior work
+
+> Ribes\*, Dunlop\*, and Mercado. *TACK: A statistical evaluation of degradation activity on a novel TArgeting Chimeras Knowledge dataset.* KDD AI for Sciences Track, 2026.
+
+---
+
+## Dataset at a Glance
+
+| Statistic | TPDdb | PROTAC-DB | PROTACpedia | **TACK** |
+|---|---|---|---|---|
+| Total records | 22,183 | 9,380 | 1,203 | **6,561** |
+| Unique PROTACs | 21,429 | 6,110 | 1,189 | **3,514** |
+| Degradation endpoints | 6,518 | 2,170 | 580 | **6,561** |
+| POI targets | 184 | 441 | 79 | **164** |
+| E3 ligases | 8 | 21 | 8 | **9** |
+| Cell lines | 142 | — | 139 | **155** |
+| Hold-out set entries | — | — | — | **913** |
+
+The dataset contains **4,184 DC₅₀** and **2,377 D**max measurements. Approximately 55% of entries are classified as active (DC₅₀ ≤ 100 nM **and** D*max* ≥ 80%).
+
+**Most represented biology:**
+- **POIs:** Androgen Receptor (26.7%), SMARCA2 (12.0%), BTK (8.9%) — top 5 account for 61.6% of endpoints
+- **E3 ligases:** CRBN and VHL together account for 98.7% of measurements
+- **Cell lines:** LNCaP (20.9%), SW1573 (15.2%), Mino (7.0%) across 155 unique lines
+
+---
+
+## Configs (Subsets)
+
+| Config | Description | Examples |
+|---|---|---|
+| `default` | All endpoints (DC₅₀ + D*max* combined) | 6,561 |
+| `DC50` | Potency measurements only | 4,184 |
+| `Dmax` | Maximal degradation efficacy only | 2,377 |
+| `multitask` | Paired DC₅₀ + D*max* for the same PROTAC/assay, also used for binary activity classification | 1,563 |
+
+---
+
+## Loading the Dataset
+
+```python
+from datasets import load_dataset
+
+# All endpoints
+ds = load_dataset("ailab-bio/TACK")
+
+# DC50 only
+ds_dc50 = load_dataset("ailab-bio/TACK", "DC50")
+
+# Dmax only
+ds_dmax = load_dataset("ailab-bio/TACK", "Dmax")
+
+# Paired multitask (DC50 + Dmax for same compound)
+ds_multi = load_dataset("ailab-bio/TACK", "multitask")
+```
+
+The `SMILES_Held_Out` column flags the structurally dissimilar held-out set (~10% of data). To reproduce the train/validation split used in the paper:
+
+```python
+ds = load_dataset("ailab-bio/TACK", "DC50")["train"]
+train_val = ds.filter(lambda x: not x["SMILES_Held_Out"])
+held_out  = ds.filter(lambda x: x["SMILES_Held_Out"])
+```
+
+---
+
+## Schema
+
+### Common columns (all configs)
+
+| Column | Type | Description |
+|---|---|---|
+| `SMILES` | string | Canonical RDKit SMILES of the PROTAC |
+| `POI_Name` | string | Gene name of the protein of interest |
+| `POI_Sequence` | string | UniProt amino acid sequence of the POI |
+| `POI_UniProt` | string | UniProt accession for the POI |
+| `Ligase_Name` | string | Name of the E3 ligase |
+| `Ligase_Sequence` | string | UniProt amino acid sequence of the E3 ligase |
+| `Ligase_UniProt` | string | UniProt accession for the E3 ligase |
+| `Cell_Line` | string | Cell line name (Cellosaurus-standardized) |
+| `Cell_Line_ID` | string | Cellosaurus identifier |
+| `Cell_Line_Species` | string | Species of origin for the cell line |
+| `Cell_Line_Description` | string | Textual description from Cellosaurus |
+| `Value` | float64 | Measured endpoint value |
+| `Value_Unit` | string | Unit of the value (nM for DC₅₀; % for D*max*) |
+| `Value_Type` | string | Endpoint type (DC50 or Dmax) |
+| `Value_Operator` | string | Comparison operator if censored (`<`, `>`, etc.) |
+| `Value_Error` | float64 | Reported measurement error (if available) |
+| `Value_Range_Min` | float64 | Lower bound for range-reported values |
+| `Value_Range_Max` | float64 | Upper bound for range-reported values |
+| `Value_Concentration` | float64 | Treatment concentration for D*max* assays |
+| `Value_Concentration_Unit` | string | Unit of treatment concentration |
+| `Value_Category` | string | Categorical activity label (where applicable) |
+| `Assay_Time` | float64 | Treatment duration in hours |
+| `Assay` | string | Standardized assay type (e.g., Western Blot, HiBit) |
+| `Modality` | string | Compound modality (PROTAC, molecular glue, etc.) |
+| `Reference` | string | Source literature or patent reference |
+| `Description` | string | Original assay description |
+| `Database` | string | Source database (TPDdb, PROTAC-DB, PROTACpedia) |
+| `TPD_ID` | string | Original identifier in the source database |
+| `POI_Cluster` | int64 | POI sequence-based cluster ID |
+| `SMILES_Scaffold_Cluster` | int64 | Murcko scaffold cluster ID (used for CV splitting) |
+| `SMILES_Butina_Cluster` | int64 | Butina/Tanimoto cluster ID |
+| `SMILES_Held_Out` | bool | **True** if this entry belongs to the structural hold-out set |
+
+The `multitask` config replaces `Value`, `Value_Unit`, etc. with `Value_DC50`, `Value_Dmax` and analogous suffixed columns, enabling simultaneous supervision on both endpoints.
+
+---
+
+## Curation Pipeline
+
+Raw data was aggregated from three repositories and cleaned through a multi-stage pipeline:
+
+1. **SMILES standardization** — canonicalization via RDKit; duplicates resolved by weighted scoring
+2. **Endpoint standardization** — DC₅₀ values converted to nM; range values converted to arithmetic mean with bounds stored; censored values (operators) preserved but flagged for exclusion from evaluation sets; categorical patent grades excluded
+3. **Protein annotation** — POI and E3 ligase names mapped to UniProt accessions; amino acid sequences retrieved from UniProt; BRD4 isoform handling applied
+4. **Cell line standardization** — validated against Cellosaurus; standardized identifiers and descriptions attached
+5. **Assay standardization** — assay descriptions parsed and normalized (e.g., "WB" → "Western Blot"); treatment concentrations extracted from metadata and free-text fields
+6. **Hold-out construction** — ~10% most structurally dissimilar PROTACs (by average Tanimoto distance using 512-bit Morgan8 fingerprints) isolated before any model training
+7. **Scaffold-based CV clustering** — remaining data grouped by Murcko scaffolds to prevent leakage between CV folds
+
+Please refer to [this link](https://github.com/ribesstefano/TACK/tree/main/tack_dataset) for the codebase used to generate the data.
+
+---
+
+## Benchmark Results
+
+Models were evaluated using **scaffold-based 5×5 repeated cross-validation** with statistical testing (Friedman + Wilcoxon + Benjamini–Hochberg correction for feature selection; Tukey HSD for architecture comparison).
+
+### Regression (hold-out set)
+
+| Task | Model | MAE | RMSE | R² | Spearman ρ |
+|---|---|---|---|---|---|
+| pDC₅₀ | MLP | 0.58 | 0.80 | **0.66** | 0.76 |
+| D*max* | XGBoost | 18.86 | 25.68 | **0.36** | 0.66 |
+
+### Binary Classification (validation folds, mean ± CI)
+
+| Model | ROC-AUC | PR-AUC | MCC | Recall @ Prec≥0.8 |
+|---|---|---|---|---|
+| **XGBoost** | **0.851** | **0.870** | **0.523** | **0.777** |
+| MLP | 0.799 | 0.824 | 0.448 | 0.600 |
+| PROTAC-STAN | 0.746 | 0.773 | 0.405 | 0.443 |
+
+All pairwise differences are statistically significant (Tukey HSD, *p* < 0.001).
+
+**Key findings:**
+- pDC₅₀ is substantially more predictable than D*max* (R² 0.66 vs. 0.36), reflecting the greater dependence of maximal degradation on cellular factors not captured by current molecular representations
+- Classical tree-based methods (XGBoost) outperform the domain-specific GNN PROTAC-STAN, consistent with the small-to-medium tabular dataset regime
+- Simple one-hot or n-gram protein encodings often match expensive ESM-S embeddings, particularly with XGBoost; ESM-S embeddings give a modest advantage for XGBoost on the classification task
+
+### Ensemble Uncertainty Quantification
+
+Ensemble standard deviation correlates positively with absolute prediction error, enabling confidence-aware compound prioritization:
+
+| Task | Method | RMSE | Spearman ρ (σ vs. \|error\|) |
+|---|---|---|---|
+| pDC₅₀ | Caruana (33 models) | 0.672 | 0.207* |
+| pDC₅₀ | Uniform avg (500 models) | 0.683 | 0.355** |
+| D*max* | Caruana (22 models) | 21.32 | 0.543** |
+| D*max* | Uniform avg (500 models) | 22.92 | 0.694** |
+
+\*\* *p* < 0.001; \* *p* < 0.01
+
+---
+
+## Best Models
+
+Pre-trained ensemble models (XGBoost and MLP, all feature configurations, 25 CV folds each) are available on Zenodo:
+
+[![Zenodo](https://img.shields.io/badge/Models-Zenodo%2015691822-blue)](https://zenodo.org/uploads/15691822)
+
+---
+
+## Citation
+
+If you use TACK in your research, please cite:
+
+```bibtex
+@misc{ribes2026tackstatisticalevaluationdegradation,
+      title={TACK: A statistical evaluation of degradation activity on a novel TArgeting Chimeras Knowledge dataset}, 
+      author={Stefano Ribes and Nils Dunlop and Rocío Mercado},
+      year={2026},
+      eprint={2605.19579},
+      archivePrefix={arXiv},
+      primaryClass={q-bio.QM},
+      url={https://arxiv.org/abs/2605.19579}, 
+}
+```
+
+---
+
+## License
+
+The TACK dataset is released under the **MIT License**. The underlying experimental data is sourced from PROTAC-DB, PROTACpedia, and TPDdb — please refer to the respective database licenses for conditions on downstream use of the original data.
+
+---
+
+## Acknowledgements
+
+SR and RM acknowledge funding from the Chalmers Gender Initiative for Excellence (Genie). RM and ND acknowledge funding from the Wallenberg AI, Autonomous Systems and Software Program (WASP), supported by the Knut and Alice Wallenberg Foundation. The authors thank Yossra Gharbi, Alexander Persson, and Felix Erngård for helpful discussions. Computations were enabled by Chalmers e-Commons and NAISS (grant 2022-06725).