openmedlab / prime

[Model] Prime

Updated on 2023.06.15

Key Features

This repository provides the official implementation of Prime (Protein language model for Intelligent Masked pretraining and Environment (temperature) prediction).

Key features:

• OGT (Optimal Growth Temperature) prediction.
• Zero-shot mutant effect prediction.

Links

• Paper
• Code

Details

What is Prime?

Prime, a novel protein language model, has been developed for predicting the Optimal Growth Temperature (OGT) and enabling zero-shot prediction of protein thermostability and activity. This novel approach leverages temperature-guided language modeling.

The performance of Prime.

Performance of the OGT prediction task.

	RMSE	Pearson correlation coefficient	Spearman's rank correlation coefficient	Coefficient of determination
Prime	4.736	0.653	0.598	0.417
DeepET	5.985	0.417	0.333	0.069

Performance of the zero-shot mutant effect prediction.

TM datasets

	ESM-1v	ROSSETA	MSA-Transformer	Prime(No OGT task)	Prime	Tranception	Prime (Fine-tuned)
1SHF-8.0	0.122	0.152	0.131	-0.028	0.131	0.247	0.453
1CSP-7.0	0.404	0.020	0.039	-0.009	0.515	0.203	0.475
1PWX-7.7	-0.046	0.158	0.010	0.595	-0.019	0.106	0.460
1PIN-7.0	0.503	0.003	0.362	-0.023	0.577	-0.138	0.665
2LZM-3.0	0.261	0.511	0.609	0.576	0.706	0.480	0.213
3UMR-7.4	0.488	0.247	0.386	0.537	0.523	0.484	0.451
1RGG-7.0	0.719	-0.066	0.212	0.327	0.725	0.562	-0.022
1BPI-7.0	0.527	0.260	0.389	0.517	0.448	0.238	0.595
2DRI-7.0	0.127	-0.602	-0.425	0.381	0.011	0.541	0.845
2LZM-5.42	0.564	0.697	0.442	0.236	0.552	-0.152	-0.107
1CF1-7.0	0.549	0.150	0.158	0.508	0.549	0.438	0.645
1AYF-8.5	0.518	-0.082	0.491	0.655	0.718	0.455	0.709
5dfr-7.8	0.568	0.457	0.425	0.507	0.439	0.346	0.839
2LZM-6.78	-0.014	0.021	0.091	-0.154	0.070	0.133	0.372
2LZM-3.05	0.484	0.463	0.816	0.387	0.613	0.608	0.734
1g5a-7.0	0.237	0.140	0.184	-0.144	0.097	0.084	0.413
1BNI-6.3	0.689	0.421	0.900	0.758	0.795	0.682	0.442
2LZM-5.4	0.179	0.492	0.475	0.401	0.544	0.631	0.673
1LRP-7.0	0.798	-0.432	0.770	0.549	0.529	0.733	-0.181
1ROP-7.0	0.257	0.805	0.605	-0.048	0.359	0.446	0.478
2LZM-5.35	0.683	0.825	0.882	0.778	0.760	0.590	0.745
1XAS-6.0	-0.259	0.329	0.203	0.028	0.014	0.420	0.832
Average	0.380	0.226	0.371	0.333	0.439	0.370	0.488

Activity datasets

	ESM-1v	MSA-transformer	Prime (No OGT task)	Prime	Tranception	Prime (fine-tuned)
BG_STRSQ	0.598	0.598	0.686	0.647	0.580	0.743
BLAT_ECOLX	0.687	0.297	0.718	0.731	0.580	0.416
TIM_SULSO	0.616	0.613	0.627	0.663	0.572	0.646
P84126_THETH	0.578	0.036	0.572	0.583	0.398	0.652
UBC9_HUMAN	0.536	0.403	0.472	0.508	0.319	0.281
AMIE_PSEAE	0.532	0.556	0.383	0.345	0.463	0.548
MTH3_HAEAESTABILIZED	0.457	0.490	0.397	0.355	0.293	0.560
B3VI55_LIPST	0.265	0.303	0.247	0.264	0.189	0.292
KKA2_KLEPN	0.174	0.121	0.177	0.182	0.105	0.178
MK01_HUMAN	0.153	0.176	0.203	0.148	0.006	0.164
RASH_HUMAN	0.125	0.174	0.119	0.129	0.107	0.155
Average	0.429	0.343	0.418	0.414	0.328	0.421

Tips

It is important to emphasize that Prime builds upon the esm2-650M framework. Specifically, we utilize the checkpoint provided by the framework to initialize the model parameters.

Get Started

Main Requirements

biopython==1.81
numpy==1.24.3
pandas==2.0.2
scipy==1.10.1
tokenizers==0.13.3
torch==1.12.0
tqdm==4.65.0
transformers==4.30.2

Installation

pip install -r requirements.txt

Download Model

prime-base

prime-fine-tuning-for-tm-datasets

Predicting OGT

python predict_ogt.py --model_name prime-base \
--fasta ./datasets/OGT/ogt_small.fasta \
--output ogt_prediction.tsv

Predicting Mutant Effect

Using the prime-base model. (Recommended)

python predict_mutant.py --model_name prime-base \
--fasta ./datasets/TM/1CF1/1CF1.fasta \
--mutant ./datasets/TM/1CF1/1CF1-7.0.tsv \
--compute_spearman \
--output pred.tsv

Or using the model that fine-tuned on the homologous sequence of the proteins in the TM dataset.

python predict_mutant.py --model_name prime-tm-fine-tuning \
--fasta ./datasets/TM/1CF1/1CF1.fasta \
--mutant ./datasets/TM/1CF1/1CF1-7.0.tsv \
--compute_spearman \
--output pred.tsv

🙋‍♀️ Feedback and Contact

• Send Email

🛡️ License

This project is under the MIT license. See LICENSE for details.

🙏 Acknowledgement

A lot of code is modified from 🤗 transformers and esm.

📝 Citation

If you find this repository useful, please consider citing this paper:

@misc{tan2023,
      title={Engineering Enhanced Stability and Activity in Proteins through a Novel Temperature-Guided Language Modeling.}, 
      author={Pan Tan and Mingchen Li and Liang Zhang and Zhiqiang Hu and Liang Hong},
      year={2023},
      eprint={2304.03780},
      archivePrefix={arXiv},
      primaryClass={q-bio.QM}
}