gbyuvd/synthaccess-chemselfies

ChemFIE-SA (ChemSELFIES - Synthesis Accessibility)

ChemFIE-SA is a BERT-like sequence classifier for predicting synthesis accessibility given a SELFIES string of a compound, fine-tuned from gbyuvd/chemselfies-base-bertmlm on DeepSA's expanded dataset from Wang et al. 2023.

Disclaimer: For Academic Purposes Only

The information and model provided is for academic purposes only. It is intended for educational and research use, and should not be used for any commercial or legal purposes. The author do not guarantee the accuracy, completeness, or reliability of the information.

Model Details

Model Description

• Model Type: Transformer (BertForSequenceClassification)
• Base model: gbyuvd/chemselfies-base-bertmlm
• Maximum Sequence Length: 512 tokens
• Number of Labels: 2 classes (0 ES: easy synthesis; 1 HS: hard to synthesize)
• Training Dataset: SELFIES with labels derived from DeepSA
• Language: SELFIES
• License: CC-BY-NC-SA 4.0

Uses

If you have Canonical SMILES instead of SELFIES, you can convert it first into a format readable by the model's tokenizer (using whitespace)

import selfies as sf

def smiles_to_selfies_sentence(smiles):
    try:
        selfies = sf.encoder(smiles)  # Encode SMILES into SELFIES
        selfies_tokens = list(sf.split_selfies(selfies))
        
        # Join dots with the nearest next tokens
        joined_tokens = []
        i = 0
        while i < len(selfies_tokens):
            if selfies_tokens[i] == '.' and i + 1 < len(selfies_tokens):
                joined_tokens.append(f".{selfies_tokens[i+1]}")
                i += 2
            else:
                joined_tokens.append(selfies_tokens[i])
                i += 1
        
        selfies_sentence = ' '.join(joined_tokens)
        return selfies_sentence
    except sf.EncoderError as e:
        print(f"Encoder Error: {e}")
        return None

# Example usage:
in_smi = "C1CCC(CC1)(CC(=O)O)CN" # Gabapentin (CID3446)
selfies_sentence = smiles_to_selfies_sentence(in_smi)
print(selfies_sentence)

"""
[C] [C] [C] [C] [Branch1] [Branch1] [C] [C] [Ring1] [=Branch1] [Branch1] [#Branch1] [C] [C] [=Branch1] [C] [=O] [O] [C] [N]

"""

Direct Use using Classifier Pipeline

You can also use pipeline:

from transformers import pipeline

classifier = pipeline("text-classification", model="gbyuvd/synthaccess-chemselfies")
classifier("[C] [C] [C] [C] [Branch1] [Branch1] [C] [C] [Ring1] [=Branch1] [Branch1] [#Branch1] [C] [C] [=Branch1] [C] [=O] [O] [C] [N]") # Gabapentin
# [{'label': 'Easy', 'score': 0.9187200665473938}]

Training Details

Training Data

Data Sources

Training data is fetched from DeepSA's repository.

Data Preparation

• SMILES is converted into SELFIES
• Chunked into three parts to accommodate Paperspace's Gradient 6hrs limit.
• Then the data was split by 90:10 ratio of train:validation.
  • 1st chunk size: 1,197,683 (1,077,915 train : 119,768 validation)
• The data contain labels for:
  • 0: Easy synthesis (requires less than 10 steps)
  • 1: Hard synthesis (requires more than 10 steps)

Training Procedure

Training Hyperparameters

• Epoch = 1 for each chunk
• Batch size = 128
• Number of steps for each chunk: 8422

I am using Ranger21 with these configuration:

Core optimizer = [madgrad](https://arxiv.org/abs/2101.11075)
Learning rate of 5e-06

num_epochs of training = ** 1 epochs **
using AdaBelief for variance computation
Warm-up: linear warmup, over 2000 iterations

Lookahead active, merging every 5 steps, with blend factor of 0.5
Norm Loss active, factor = 0.0001
Stable weight decay of 0.01
Gradient Centralization = On

Adaptive Gradient Clipping = True
    clipping value of 0.01
    steps for clipping = 0.001

1st Chunk:

Step	Training Loss	Validation Loss	Accuracy	Precision	Recall	F1	Roc Auc
8420	0.128700	0.128632	0.922860	0.975201	0.867836	0.918391	0.990007

Model Evaluation

Testing Data

The model (currently only trained on the 1st chunk) was evaluated using four test sets provided by DeepSA's authors (Wang et al. 2023) to ensure comprehensive performance assessment across various scenarios:

1. Main Expanded Test Set

2. Independent Test Set 1 (TS1)

   • Characteristics: Contains ES and HS compounds with high intra-group fingerprint similarity, but significant inter-group pattern differences.

3. Independent Test Set 2 (TS2)

   • Characteristics: Contains a small portion of ES and HS molecules showing similar fingerprint patterns.

4. Independent Test Set 3 (TS3)

   • Characteristics: All compounds exhibit high fingerprint similarity, presenting the most challenging classification task.

Evaluation Metrics

A comprehensive set of metrics employed to evaluate the model's performance:

1. Accuracy (ACC)
2. Recall
3. Precision
4. F1
5. Area Under the Receiver Operating Characteristic curve (AUROC)

All metrics were evaluated using a threshold of 0.50 for binary classification.

Results

Below are the detailed results of our model's performance across all test sets:

Expanded Test Set Results

Comparison data is sourced from Wang et al. (2023), used various models as encoding layer:

• bert-mini (MinBert)
• bert-tiny (TinBert)
• roberta-base (RoBERTa)
• deberta-v3-base (DeBERTa)
• Chem_GraphCodeBert (GraphCodeBert)
• electra-small-discriminator (SmELECTRA)
• ChemBERTa-77M-MTR (ChemMTR)
• ChemBERTa-77M-MLM (ChemMLM)

which was trained/fine-tuned to predict based on SMILES - while ChemFIE-SA is SELFIES-based:

Model	Recall	Precision	F1	AUROC
DeepSA_DeBERTa	0.873	0.920	0.896	0.959
DeepSA_GraphCodeBert	0.931	0.944	0.937	0.987
DeepSA_MinBert	0.933	0.945	0.939	0.988
DeepSA_RoBERTa	0.940	0.940	0.940	0.988
DeepSA_TinBert	0.937	0.947	0.942	0.990
DeepSA_SmELECTRA	0.938	0.949	0.943	0.990
ChemFIE-SA	0.952	0.942	0.947	0.990
DeepSA_ChemMLM	0.955	0.967	0.961	0.995
DeepSA_ChemMTR	0.968	0.974	0.971	0.997

TS1-3 Results

Comparison with DeepSA_SmELECTRA as described in Wang et al. (2023):

Datasets	Model	ACC	Recall	Precision	F1	AUROC	Threshold
TS1	DeepSA	0.995	1.000	0.990	0.995	1.000	0.500
	ChemFIE-SA	0.996	1.000	0.992	0.996	1.000	0.500
TS2	DeepSA	0.838	0.730	0.871	0.795	0.913	0.500
	ChemFIE-SA	0.805	0.775	0.770	0.773	0.886	0.500
TS3	DeepSA	0.817	0.753	0.864	0.805	0.896	0.500
	ChemFIE-SA	0.731	0.642	0.781	0.705	0.797	0.500

Model Examination

You can visualize its attention heads using BertViz and attribution weights using Captum - as done in the base model in Interpretability section.

Compute Infrastructure

Hardware

• Platform: Paperspace's Gradients
• Compute: Free-P5000 (16 GB GPU, 30 GB RAM, 8 vCPU)

Software

• Python: 3.9.13
• Transformers: 4.42.4
• PyTorch: 2.3.1+cu121
• Accelerate: 0.32.0
• Datasets: 2.20.0
• Tokenizers: 0.19.1
• Ranger21: 0.0.1
• Selfies: 2.1.2

Citation

If you find this project useful in your research and wish to cite it, please use the following BibTex entry:

@software{chemfie_basebertmlm,
  author = {GP Bayu},
  title = {{ChemFIE Base}: Pretraining A Lightweight BERT-like model on Molecular SELFIES},
  url = {https://huggingface.co/gbyuvd/chemselfies-base-bertmlm},
  version = {1.0},
  year = {2024},
}

References

DeepSA

@article{Wang2023DeepSA,
  title={DeepSA: a deep-learning driven predictor of compound synthesis accessibility},
  author={Wang, Shihang and Wang, Lin and Li, Fenglei and Bai, Fang},
  journal={Journal of Cheminformatics},
  volume={15},
  pages={103},
  year={2023},
  month={Nov},
  publisher={BioMed Central},
  doi={10.1186/s13321-023-00771-3},
}

SELFIES

@article{krenn2020selfies,
  title={Self-referencing embedded strings (SELFIES): A 100\% robust molecular string representation},
  author={Krenn, Mario and H{\"a}se, Florian and Nigam, AkshatKumar and Friederich, Pascal and Aspuru-Guzik, Alan},
  journal={Machine Learning: Science and Technology},
  volume={1},
  number={4},
  pages={045024},
  year={2020},
  doi={10.1088/2632-2153/aba947}
}

Ranger21

@article{wright2021ranger21,
      title={Ranger21: a synergistic deep learning optimizer}, 
      author={Wright, Less and Demeure, Nestor},
      year={2021},
      journal={arXiv preprint arXiv:2106.13731},
}

Contact & Support My Work

G Bayu (gbyuvd@proton.me)

This project has been quiet a journey for me, I’ve dedicated hours on this and I would like to improve myself, this model, and future projects. However, financial and computational constraints can be challenging.

If you find my work valuable and would like to support my journey, please consider supporting me here. Your support will help me cover costs for computational resources, data acquisition, and further development of this project. Any amount, big or small, is greatly appreciated and will enable me to continue learning and explore more.

Thank you for checking out this model, I am more than happy to receive any feedback, so that I can improve myself and the future model/projects I will be working on.