DIONYSUS: Calibration and generalizability of probabilistic models on low-data chemical datasets

This package is accompanied by this paper: Calibration and generalizability of probabilistic models on low-data chemical datasets with DIONYSUS.

Authors: Gary Tom, Riley J. Hickman, Aniket Zinzuwadia, Afshan Mohajeri, Benjamin Sanchez-Lengeling, Alan Aspuru-Guzik. (2022)

Preliminary

DIONYSUS requires the following:

• Python >= 3.8
• rdkit >= 2021.03.3
• tensorflow == 2.9.0
• tensorflow-probability == 0.17.0
• tf-models-official == 2.7.1
• graph_nets == 1.1.0
• sonnet == 2.0.0
• ngboost == 0.3.12
• gpflow == 2.5.2
• scikit-learn == 1.0.2
• scikit-multilearn == 0.2.0
• mordred == 1.2.0
• dask == 2022.6.1
• umap-learn == 0.5.1
• cairosvg == 2.5.2
• pandas == 1.4.1
• seaborn == 0.11.2
• hdbscan == 0.8.27

Datasets

Datasets used are shown in data/ directory. For new datasets, simply add it to data/raw/, and the corresponding information in data/dataset_registry_raw.csv. The following information is required:

• name: name of dataset
• shortname: name that will be referenced in the scripts
• filename: the csv file name ({shortname}.csv)
• task: either regression/binary (classification)
• smiles_column: name of column containing the smiles representations
• target_columns: name of column containing the target of interest

Usage

Preprocessing

Scripts to preprocess the datasets are in scripts/ directory. Please run these prior to any of the below experiments.

cd scripts/

# prepare molecules and analysis directory in data/{shortname}
# canonicalize all smiles 
# removes all invalid and duplicate smiles
# removes all smiles with salts, ions or fragments
python make_qsar_ready.py --dataset={shortname} 

# create splits and features
# create all features used (mfp, mordred, graphtuple, graphembed)
# create the train/val/test splits used
python make_features.py --dataset={shortname} 

Experiment 1: Supervised learning

Scripts to run experiments are contained in scripts/ directory.

cd scripts/

# make all predictions for specified feature/model
python make_predictions.py --dataset={shortname} --model={modelname} --feature={featurename} 

# create evaluations/figures for all available prediction data
python make_evaluations.py --dataset={shortname}

Experiment 2: Bayesian optimization

Scripts are found in bayes_opt/ directory.

All results will be contained in data/{shortname}/bayesian_optimization.

cd bayes_opt/

# run the bayesian optimization campaign
python make_bo.py --dataset={shortname} --num_restarts=30 --budget=250 --goal=minimize --frac_init_design=0.05

# create the traces and evaluation files
# also outputs files with the fraction of hits calculated
python make_bo_traces.py --dataset={shortname}

Experiment 3: Cluster splits and generalizability

Similar to the first experiment, the scripts are found in scripts/ directory. Once datasets are cleaned and features are made, you can make the cluster splits, and run for specified feature/model. In the manuscript, we only do this for mordred/GPs.

All results will be contained in data/{shortname}/generalization.

cd scripts/

# create the cluster splits
python make_generalization_splits.py --dataset={shortname} 

# create evaluations for all available prediction data
python make_generalization_predictions.py --dataset={shortname}

# evaluate the predictions on each cluster split, and generate plots
python make_generalization_evaluations.py --dataset={shortname}

Proposed structure of repository (TODO)

Structure of repository

• mol_data: dataset preprocessor and loader. And be extended to other datasets and new features.
• dionysus: model-agnostic evaluation script and library. Just requires predictions.
• dionysus_addons: models used in the paper, here for reproducibility.

...