DEL QSAR

Prediction of enrichment from molecular structure, using DNA-encoded libraries and machine learning with a probabilistic loss function

Dependencies

• Python (3.6.10)
• chemprop (0.0.2)
• Numpy (1.18.5)
• pandas (1.0.4)
• PyTorch (1.5.0)
• RDKit (2020.03.2)
• scikit-learn (0.23.1)
• tqdm (4.46.1)
• h5py (2.10.0; for writing/reading an HDF5 file with stored fingerprints)
• Optuna (1.5.0; for hyperparameter optimization)
• hickle (3.4.5; for saving/loading dictionaries in the bit and substructure analysis)

Instructions

Initial set-up

• Unzip triazine_lib_sEH_SIRT2_QSAR.csv.gz in the experiments/datasets folder
• Unzip pubchem_smiles.npy.gz in the experiments/visualizations folder
• To generate and save molecular fingerprints to an HDF5 file, navigate to the experiments folder and run:

python fps_preprocessing.py --csv </path/to/data.csv from experiments/datasets folder> --fps_h5 <filename for HDF5 file to create> --fp_size <fingerprint size (number of bits)>

Training and evaluating models

To train/evaluate models, navigate to the experiments folder. The following is a general command for running one of the scripts:

python <script_name.py> --csv </path/to/data.csv from experiments/datasets folder> --out <experiment label (name of results subfolder to create)> --device <device (set to cuda:0 if using GPU)>

Additional command-line arguments include:

• --exp <column header(s) for barcode counts in experiment with protein(s) of interest>
  • Replace spaces with underscores
• --beads <column header(s) for barcode counts in beads-only control without protein(s) of interest>
  • Specify beads column header for each protein of interest, in the same order as listed in --exp
  • Replace spaces with underscores

The script depends on the dataset/model type/task. Further details are provided below, including more specific command-line arguments.

Regression models and binary classifiers:

Scripts:

• General:
  • single_model_run.py (training and evaluating a model with user-provided hyperparameter values)
• For DD1S CAIX dataset:
  • hyperparameter_optimization_DD1S_CAIX_FFN.py (optimizing feed-forward neural networks)
  • hyperparameter_optimization_DD1S_CAIX_MPN.py (optimizing directed message passing neural networks)
• For triazine sEH and SIRT2 datasets:
  • hyperparameter_optimization_triazine_FFN.py (optimizing feed-forward neural networks)
  • triazine_MPN_LR_tuning.py (tuning learning rate for directed message passing neural networks)
  • triazine_MPN.py (training and evaluating directed message passing neural networks)

Additional command-line arguments include:

• --featurizer <type of molecule featurization>
  • For feed-forward neural networks: 'fingerprint' or 'onehot'
  • For directed message passing neural networks: 'graph'
• --splitter <type of data split for train/validation/test>
  • Options include:
  • 'random'
  • any combination of 'cycle1', 'cycle2', 'cycle3' (for example: 'cycle1','cycle3')
  • To reproduce results for cycle splits along multiple cycles, list the cycles in ascending numerical order
• --seed <random seed for data splitting and weight initialization>
• --task_type <task type>
  • Options include:
  • 'regression'
  • 'classification'
• --loss_fn_train <loss function to use during training>
  • For binary classifiers: 'BCE'
  • Options for regression models include:
  • 'nlogprob' (probabilistic loss function)
  • 'MSE' (mean squared error)
• --max_epochs <maximum number of epochs>
  • Values for reproducing results:
  • Training feed-forward neural networks: 1000 for DD1S CAIX dataset; 300 for triazine sEH and SIRT2 datasets
  • Training directed message passing neural networks: 100
• --patience <patience>
  • To reproduce results, set to 5
• --max_norm <max norm>
  • To reproduce results, set to 5

For fingerprint featurization (if reading from an HDF5 file with stored fingerprints):

• --fps_h5 </path/to/file_with_stored_fingerprints.h5 from experiments folder>

For hyperparameter optimization (including triazine_MPN_LR_tuning.py):

• --n_trials <number of trials to run/hyperparameter sets to try>
  • Values for reproducing results:
  • For the DD1S CAIX dataset: 100
  • For the triazine sEH and SIRT2 datasets: 25 for feed-forward neural networks, 4 for directed message passing neural networks

For single_model_run.py:

• --model_type <model type>
  • Options include:
  • 'MLP' (feed-forward neural network)
  • 'MoleculeModel' (directed message passing neural network)
• --lr <initial learning rate>
• --dropout <dropout rate>
• --eval_metric <loss function used to evaluate the model>
  • Options include:
  • 'NLL' (negative log-likelihood)
  • 'MSE' (mean-squared error)
• For feed-forward neural network:
  • --layer_sizes <hidden layer sizes>
• For directed message passing neural network:
  • --depth <number of message-passing steps>
  • --hidden_size <size of hidden layers>
  • --ffn_num_layers <number of feed-forward network layers>

For directed message passing neural networks:

• --num_workers <number of workers for loading data>

For directed message passing neural networks specifically on the triazine sEH and SIRT2 datasets:

• --depth <number of message-passing steps>
• --hidden_size <size of hidden layers>
• --ffn_num_layers <number of feed-forward network layers>

For triazine_MPN.py:

• --lr <initial learning rate>
• --dropout <dropout rate>

For binary classifiers:

• --threshold_type <type of threshold for determining ground truth labels>
  • Options include:
  • 'percentile'
  • 'fixed'
  • To reproduce results, set to 'percentile'
• --threshold_val <threshold value; percentile or exact value>
  • Percentile example: 99.5 to define the top 0.5% of training set compounds as enriched

Evaluating trained regression models as binary classifiers, or using MSE loss/rank correlation coefficient

Scripts:

• bin_eval.py (fixed threshold)
• bin_eval_multiple_thresholds.py (multiple thresholds)
• mse_loss_eval.py
• rank_corr_coeff_eval.py

These scripts require (1) an experiments/models folder with saved regression models (.torch files) organized by dataset/model type and named by data split/seed, as follows (for brevity, only filenames for the random splits are shown; cycle-split models should also be included, replacing random with cycle1, ..., cycle12, ..., cycle123 in the filename):

└── models
    ├── DD1S_CAIX
    │   └── D-MPNN
    │   │   └── random_seed_0.torch 
    │   │   └── random_seed_1.torch
    │   │   └── random_seed_2.torch
    │   │   └── random_seed_3.torch
    │   │   └── random_seed_4.torch
    │   │   
    │   └── D-MPNN_pt
    │   │   └── (same as for models/DD1S_CAIX/D-MPNN)
    │   │
    │   └── FP-FFNN
    │   │   └── (same as for models/DD1S_CAIX/D-MPNN)
    │   │
    │   └── FP-FFNN_pt
    │   │   └── (same as for models/DD1S_CAIX/D-MPNN)
    │   │
    │   └── OH-FFNN
    │   │   └── (same as for models/DD1S_CAIX/D-MPNN)
    │   │
    │   └── OH-FFNN_pt
    │       └── (same as for models/DD1S_CAIX/D-MPNN)
    │    
    ├── triazine_sEH
    │   └── D-MPNN
    │   │   └── random_seed_0.torch
    │   │   └── random_seed_1.torch
    │   │   └── random_seed_2.torch
    │   │ 
    │   └── D-MPNN_pt
    │   │   └── (same as for models/triazine_sEH/D-MPNN)
    │   │
    │   └── FP-FFNN
    │   │   └── random_seed_0.torch
    │   │   └── random_seed_1.torch
    │   │   └── random_seed_2.torch
    │   │   └── random_seed_3.torch
    │   │   └── random_seed_4.torch
    │   │   
    │   └── FP-FFNN_pt
    │   │   └── (same as for models/triazine_sEH/FP-FFNN)
    │   │  
    │   └── OH-FFNN
    │   │   └── (same as for models/triazine_sEH/FP-FFNN)
    │   │  
    │   └── OH-FFNN_pt
    │       └── (same as for models/triazine_sEH/FP-FFNN)
    │
    ├── triazine_SIRT2
    │   └── (same as for models/triazine_sEH)
    │
    └── triazine_sEH_SIRT2_multi-task
        └── D-MPNN
        │   └── random_seed_0.torch
        │   └── random_seed_1.torch
        │   └── random_seed_2.torch
        │
        └── FP-FFNN
        │   └── random_seed_0.torch
        │   └── random_seed_1.torch
        │   └── random_seed_2.torch
        │   └── random_seed_3.torch
        │   └── random_seed_4.torch
        │
        └── OH-FFNN
            └── (same as for models/triazine_sEH_SIRT2_multi-task/FP-FFNN)

(2) a csv with the hyperparameter values of the saved models, formatted like the following (example values are shown):

dataset	model type	seed	split	layer sizes	dropout	depth	hidden size	FFN num layers
DD1S_CAIX	D-MPNN	0	random		0.1	6	1300	3
triazine_sEH	FP-FFNN_pt	1	random	128, 128	0.35
triazine_SIRT2	OH-FFNN	1	random	512, 256, 128	0.45

For each of the above scripts, each run evaluates all regression models (only on random splits for evaluating models as binary classifiers) for a given dataset and model type. bin_eval.py and bin_eval_multiple_thresholds.py evaluate the models as binary classifiers; mse_loss_eval.py evaluates models using MSE loss; rank_corr_coeff_eval.py evaluates models using Spearman's rank correlation coefficient.

Additional command-line arguments include:

• --model_type <model type>
  • Options include:
  • 'D-MPNN'
  • 'D-MPNN_pt'
  • 'FP-FFNN'
  • 'FP-FFNN_pt'
  • 'OH-FFNN'
  • 'OH-FFNN_pt'
• --hyperparams </path/to/hyperparameter_values_of_saved_models.csv from experiments folder>

For D-MPNN and D-MPNN_pt models:

• --num_workers <number of workers for loading data>

Specifically for bin_eval.py and bin_eval_multiple_thresholds.py:

• --random_split_only <True or False>
  • Whether to evaluate the models for random split only
  • To reproduce results, set to True
• --random_guess <True or False>
  • Whether to generate random-guess baseline (instead of evaluating saved models)
  • To reproduce results, set --model_type to 'FP-FFNN' when generating random-guess baseline
• --threshold_type <type of threshold for determining ground truth labels>
  • Options include:
  • 'percentile'
  • 'fixed'
  • To reproduce results, set to 'percentile'
• --threshold_val <threshold value; percentile or exact value>
  • Percentile example: 99.5 to define the top 0.5% of training set compounds as enriched

Specifically for bin_eval_multiple_thresholds.py:

• --num_thresholds <number of (logarithmically spaced) thresholds to try>
  • To reproduce results, set to 20
• --start_idx <threshold index, from 0 to 19, to start at>
  • Can set to 1 or higher if resuming a job
• --stop_idx <threshold index, from 1 to 20, to stop at>
  • Can set to 19 or lower if stopping early

KNN and random baselines

(1) To train and evaluate baseline k-nearest-neighbors (KNN) regression models, run the following scripts for each dataset:

• For the DD1S CAIX dataset:
  • Run knn_train_DD1S_CAIX.py, specifying the type of molecule featurization (--featurizer <'onehot' or 'fingerprint'>) and the number of neighbors (--n_neighbors <number of neighbors; values of 1, 3, 5, 7, 9 were tested>). The script iterates through all data splits and random seeds, and saves the trained models in the results folder.
  • Create the folders experiments/models/DD1S_CAIX/OH-KNN (for the onehot KNNs) and experiments/models/DD1S_CAIX/FP-KNN (for the fingerprint-based KNNs), with subfolders k_1, k_3, k_5, k_7, k_9 (for the different tested values of n_neighbors); move the corresponding saved models (.joblib files) to these folders. The filename for each saved model should be of the form <data split>_seed_<random seed>.joblib, where the possible data split names arerandom, cycle1, ..., cycle12, ..., cycle123.
  • Run DD1S_CAIX_knn_eval.py, specifying the metric used for evaluation (--eval_metric <'NLL', 'MSE', or 'rank_corr_coeff'>), the type of featurization (--featurizer <'onehot' or 'fingerprint'>), the data split (--splitter), and random seed (--seed). The script iterates through all tested n_neighbors values of 1, 3, 5, 7, 9.
• For the triazine datasets:
  • Run knn_train_triazine.py, specifying the type of molecule featurization (--featurizer <'onehot' or 'fingerprint'>), data split (--splitter), and random seed (--seed). To reproduce results, keep the default value of 9 for --n_neighbors. The script saves the trained model in the results folder.
  • Create the folders experiments/models/<dataset>/OH-KNN/k_9 and experiments/models/<dataset>/FP-KNN/k_9 (where <dataset> is triazine_sEH or triazine_SIRT2, and the subfolder k_9 refers to the fixed value of 9 for n_neighbors); move the corresponding saved models (.joblib files) to these folders. KNNs were trained only for random seed 0 on the triazine datasets; the filename for each saved model should be of the form <data split>_seed_0.joblib.
  • Run triazine_knn_generate_test_preds.py to generate and save test-set predictions, specifying the metric used for evaluation (--eval_metric <'NLL', 'MSE', or 'rank_corr_coeff'>), the type of featurization (--featurizer <'onehot' or 'fingerprint'>), the data split (--splitter), and random seed (--seed). The script uses 9 as the value for n_neighbors. The generated test-set predictions are saved in the results folder.
  • Run triazine_knn_eval_on_test_preds.py, specifying the path to the saved test-set predictions (from the /experiments/results folder), the metric used for evaluation (--eval_metric <'NLL', 'MSE', or 'rank_corr_coeff'>), and the data split (--splitter).

(2) To run random baselines, run the script random_baseline.py, specifying via --hyperparams the filename of a csv (in the experiments folder) with the hyperparameter values of the saved models (for the specific format of the hyperparameters file, see (2) under "Evaluating trained regression models as binary classifiers, or using MSE loss/rank correlation coefficient"). Also specify the data split (--splitter), the type of random baseline (--random_type <'shuffle_preds' or 'predict_all_ones'>), and the metric used for model evaluation (--eval_metric <'NLL', 'MSE', or 'rank_corr_coeff'>).

Visualizations

Scripts and notebooks for visualizations can be found in the experiments/visualizations folder

Atom-centered Gaussian visualizations for fingerprint-based models

To visualize atomic contributions to the predictions of a trained fingerprint-based model, run:

python visualize_smis.py --model_path </path/to/saved_model.torch from experiments folder> --cpd_ids <compound ID(s) of the compound(s) to visualize> --csv </path/to/data.csv from experiments/datasets folder> --fps_h5 </path/to/file_with_stored_fingerprints.h5 from experiments folder> --out <label for results subfolder> --layer_sizes <hidden layer sizes> --dropout <dropout rate>

where --layer_sizes and --dropout are hyperparameters of the saved model

Bit and substructure analysis

This visualization requires:

• (i) a file with stored fingerprints for the DD1S CAIX dataset (for instructions, see the "Initial set-up" section above)
• (ii) a file with stored fingerprints for the triazine library (for instructions, see the "Initial set-up" section above)
• (iii) saved random split FP-FFNN models; model hyperparameter values (including learning rate) are specified in compiled_results.xlsx in the experiments/paper_results folder
  • DD1S CAIX (seeds 0, 1, 2)
  • triazine sEH (seed 0)
  • triazine SIRT2 (seed 0)

To run the visualization, run all cells in Single substructure analysis.ipynb and Substructure pair analysis.ipynb (note: the substructure pair analysis depends on results from running the single substructure analysis).

Fingerprint and model filenames/paths, etc. may be modified as necessary in the fourth cell from the top in each of the Jupyter notebooks. Information about the bits and substructures is printed out in the notebook; visualizations of the substructures are saved to png files, along with histograms and bar graphs.

For each dataset in the single substructure analysis, a command-line alternative to running the first two cells under "Get and visualize substructures" is to run:

python single_substructure_analysis_get_substructures.py --csv </path/to/data.csv from experiments/datasets folder> --fps_h5 </path/to/file_with_stored_fingerprints.h5 from experiments folder> --dataset_label <'DD1S_CAIX', 'triazine_sEH', or 'triazine_SIRT2'> --seed <random seed for data splitting and weight initialization (only used for file naming in this context)> --bits_of_interest <bits of interest (top 5 and bottom 3 bits)>

After running this script, the rest of the single substructure analysis for the given dataset can be resumed in the Jupyter notebook, starting with the third cell (currently commented-out) under "Get and visualize substructures."

UMAP

1. Navigate to the experiments/visualizations folder
2. Generate 4096-bit fingerprints for the PubChem compounds (see pubchem_smiles.npy for the compounds' SMILES strings) by running python generate_pubchem_fps.py. Also generate 4096-bit fingerprints for DOS-DEL-1 and the triazine library, using the script fps_preprocessing.py in the experiments folder (for instructions, see the "Initial set-up" section above). The resulting files with stored fingerprints should be moved to the experiments/visualizations folder.
3. To train and apply a UMAP embedding, run:

python UMAP.py --num_threads <number of threads> --pubchem_fps_h5 <name of HDF5 file with stored 4096-bit fingerprints for PubChem> --DD1S_fps_h5 <name of HDF5 file with stored 4096-bit fingerprints for DOS-DEL-1> --triazine_fps_h5 <name of HDF5 file with stored 4096-bit fingerprints for the triazine library>

4. To generate UMAP plots, run all cells in UMAP plots.ipynb

Various plots

• Loss function plots
  • Run all cells in Loss function plots.ipynb
• Test performance bar graphs/scatter plots
  • Requires csv files DD1S_CAIX_NLL_test_losses.csv, DD1S_CAIX_MSE_test_losses.csv, DD1S_CAIX_rank_corr_coeffs.csv, triazine_sEH_NLL_test_losses.csv, triazine_sEH_MSE_test_losses.csv, triazine_sEH_rank_corr_coeffs.csv, triazine_SIRT2_NLL_test_losses.csv, triazine_SIRT2_MSE_test_losses.csv, triazine_SIRT2_rank_corr_coeffs.csv, triazine_multitask_sEH_test_losses.csv, and triazine_multitask_SIRT2_test_losses.csv in the experiments folder
  • For the single-task model NLL/MSE/rank correlation coefficient csv files, the column headers should be model type, (seed), split (data split names recorded as random, cycle1, ..., cycle12, ..., cycle123), and test performance (loss or rank correlation coefficient on the test set). The model type names should be recorded as OH-FFNN, OH-FFNN_pt, FP-FFNN, FP-FFNN_pt, D-MPNN, and D-MPNN_pt
  • For the multi-task model test loss csv files (which should include test losses for both the multi-task models and the corresponding single-task models), the column headers should be model type, (seed), split (data split names recorded as random, cycle123), and test performance (loss on the test set). The model type names should be recorded as OH-FFNN_single-task, FP-FFNN_single-task, D-MPNN_single-task, OH-FFNN_multi-task, FP-FFNN_multi-task, and D-MPNN_multi-task
  • Run all cells in Test performance bar graphs and scatter plots.ipynb
• DD1S CAIX hyperparameter optimization result histograms

  • Requires two csv files DD1S_CAIX_hyperparameter_optimization_results.csv (for the D-MPNN / D-MPNN_pt regression models) and bin_DD1S_CAIX_hyperparameter_optimization_results.csv (for the random split D-MPNN binary classifiers) in the experiments folder, each formatted like the following (example values are shown):

    model type	seed	split	depth	FFN num layers	hidden size	dropout
    D-MPNN	0	random	6	3	1300	0.10

  • Run all cells in DD1S CAIX hyperparameter optimization result histograms.ipynb in the experiments folder

• DD1S CAIX KNN n_neighbors optimization result histograms
  • Requires a csv file DD1S_CAIX_KNN_k_optimization_results.csv in the experiments folder, with column headers model type (OH-KNN or FP-KNN), seed (0, 1, 2, 3, or 4), metric (NLL, MSE, or rank corr coeff), split (random, cycle1, ..., cycle12, ..., cycle123), and k (optimized number of neighbors)
  • Run all cells in DD1S CAIX KNN k optimization result histograms.ipynb
• DD1S CAIX histograms (1D and 2D) and parity plots; includes plots for both NLL- and MSE-trained models
  • Requires:
  • (i) a file with stored fingerprints for the DD1S CAIX dataset (for instructions, see the "Initial set-up" section above)
  • (ii) two NLL-trained FP-FFNN models (random split, cycle 1+2 split) and one MSE-trained FP-FFNN (random split); model hyperparameter values (including learning rate) are specified in compiled_results.xlsx in the experiments/paper_results folder
  • Run all cells in DD1S CAIX histograms and parity plots.ipynb (can modify fingerprint and model filenames/paths as necessary, in the fourth cell from the top)
• DD1S CAIX disynthon plots
  • Requires:
  • (i) a file with stored fingerprints for the DD1S CAIX dataset (for instructions, see the "Initial set-up" section above)
  • (ii) a random split FP-FFNN model; model hyperparameter values (including learning rate) are specified in compiled_results.xlsx in the experiments/paper_results folder
  • Run all cells in DD1S CAIX disynthon parity plots and 1D histograms.ipynb (can modify fingerprint and model filenames/paths as necessary, in the fourth cell from the top)
• Triazine sEH / SIRT2 parity plots
  • Requires:
  • (i) a file with stored fingerprints for the triazine library (for instructions, see the "Initial set-up" section above)
  • (ii) two saved random split FP-FFNN models (triazine sEH, triazine SIRT2); model hyperparameter values (including learning rate) are specified in compiled_results.xlsx in the experiments/paper_results folder
  • Run all cells in Triazine parity plots.ipynb (can modify fingerprint and model filenames/paths as necessary, in the fourth cell from the top)
• Triazine sEH / SIRT2 disynthon parity plots
  • Requires:
  • (i) a file with stored fingerprints for the triazine library (for instructions, see the "Initial set-up" section above)
  • (ii) two saved random split FP-FFNN models (triazine sEH, triazine SIRT2); model hyperparameter values (including learning rate) are specified in compiled_results.xlsx in the experiments/paper_results folder
  • Run all cells in Triazine disynthon parity plots.ipynb (can modify fingerprint and model filenames/paths as necessary, in the fourth cell from the top)
• Distributional shift histograms
  • Run all cells in DD1S CAIX cycle 2 distributional shift.ipynb
• Binary classification baseline comparison bar graphs (fixed threshold)
  • Requires a csv file bin_AUCs.csv in the experiments folder. Column headers should be dataset, model type, seed, PR AUC, and ROC AUC; datasets should be recorded as DD1S CAIX, triazine sEH, triazine SIRT2; model types should be recorded as OH-FFNN, OH-FFNN pt, OH-FFNN bin, FP-FFNN, FP-FFNN pt, FP-FFNN bin, D-MPNN, D-MPNN pt, D-MPNN bin, Random guess
  • Run all cells in Fixed threshold bin plots.ipynb
• Binary classification baseline comparison line graphs (multiple thresholds)
  • Requires a csv file AUCs_multiple_thresholds.csv in the experiments folder. Column headers should be dataset, model type, top percent, seed, PR AUC, and ROC AUC; datasets should be recorded as DD1S CAIX, triazine sEH, triazine SIRT2; model types should be recorded as OH-FFNN, OH-FFNN pt, FP-FFNN, FP-FFNN pt, D-MPNN, D-MPNN pt, Random guess; a top percent value of x (for example) means that the top x% of training set compounds are defined as enriched.
  • Run all cells in Multiple thresholds bin plots.ipynb
• 2D histograms of predicted vs. calculated enrichment for triazine sEH and SIRT2 datasets
  • Requires:
  • (i) a file with stored fingerprints for the triazine library (for instructions, see the "Initial set-up" section above)
  • (ii) four saved FP-FFNN models (triazine sEH + random split, triazine sEH + cycle 1+2+3 split, triazine SIRT2 + random split, triazine SIRT2 + cycle 1+2+3 split); model hyperparameter values (including learning rate) are specified in compiled_results.xlsx in the experiments/paper_results folder
  • Run all cells in Triazine 2D histograms.ipynb (can modify fingerprint and model filenames/paths as necessary, in the fourth cell from the top)
• Parity plots to evaluate generalization ability
  • Requires:
  • (i) a file with stored fingerprints for the triazine library (for instructions, see the "Initial Set-up" section above)
  • (ii) saved cycle 1+2+3 models (one for each (triazine dataset, model type, replicate/seed) triple, where the included model types are FP-FFNN, OH-FFNN, and D-MPNN); model hyperparameter values (including learning rate) are specified in compiled_results.xlsx in the experiments/paper_results folder
  • Run all cells in Triazine generalization parity plots.ipynb (can modify fingerprint and model filenames/paths as necessary, in the fourth cell from the top)

Outliers for the DD1S CAIX dataset

1. To train a FP-KNN on the entire dataset, run FP-KNN_train_on_all_DD1S_CAIX.py (specify a filename for the results folder with --out; otherwise, leave the command-line arguments as the default values). The script saves the trained model in a subfolder of the results folder.
2. To walk through the process used to identify example outliers in the DD1S CAIX dataset, see Identifying DD1S CAIX outliers.ipynb in the experiments folder
3. Run DD1S_CAIX_outliers_get_nearest_neighbor.py (use --model_path to specify the path, from the experiments folder, to the saved FP-KNN trained on the entire DD1S CAIX dataset) to obtain the index and SMILES string of the nearest neighbor in the DD1S CAIX dataset for each example outlier