├── .gitignore ├── Dockerfile ├── LICENSE ├── README.md ├── data ├── Test_seed1.fasta ├── Test_seed1_aligned.aln └── per_protein_embeddings.h5.zip ├── docker-compose.yml ├── img ├── fine-tuning.png ├── gpu.png ├── logo_small.gif ├── nb_logo.png └── protgpt2.png ├── notebooks ├── embeddings.ipynb ├── model_training.ipynb ├── prediction.ipynb ├── prot_design.ipynb └── seq_analysis.ipynb ├── poetry.lock ├── pyproject.toml ├── ran ├── embeddings.html ├── model_training.html ├── prediction.html ├── prot_design.html └── seq_analysis.html ├── requirements.txt ├── slides ├── intro_pLM.key └── intro_pLM.pdf └── topics.md /.gitignore: -------------------------------------------------------------------------------- 1 | # Byte-compiled / optimized / DLL files 2 | __pycache__/ 3 | *.py[cod] 4 | *$py.class 5 | 6 | # C extensions 7 | *.so 8 | 9 | # Distribution / packaging 10 | .Python 11 | build/ 12 | develop-eggs/ 13 | dist/ 14 | downloads/ 15 | eggs/ 16 | .eggs/ 17 | lib/ 18 | lib64/ 19 | parts/ 20 | sdist/ 21 | var/ 22 | wheels/ 23 | share/python-wheels/ 24 | *.egg-info/ 25 | .installed.cfg 26 | *.egg 27 | MANIFEST 28 | 29 | # PyInstaller 30 | # Usually these files are written by a python script from a template 31 | # before PyInstaller builds the exe, so as to inject date/other infos into it. 32 | *.manifest 33 | *.spec 34 | 35 | # Installer logs 36 | pip-log.txt 37 | pip-delete-this-directory.txt 38 | 39 | # Unit test / coverage reports 40 | htmlcov/ 41 | .tox/ 42 | .nox/ 43 | .coverage 44 | .coverage.* 45 | .cache 46 | nosetests.xml 47 | coverage.xml 48 | *.cover 49 | *.py,cover 50 | .hypothesis/ 51 | .pytest_cache/ 52 | cover/ 53 | 54 | # Translations 55 | *.mo 56 | *.pot 57 | 58 | # Django stuff: 59 | *.log 60 | local_settings.py 61 | db.sqlite3 62 | db.sqlite3-journal 63 | 64 | # Flask stuff: 65 | instance/ 66 | .webassets-cache 67 | 68 | # Scrapy stuff: 69 | .scrapy 70 | 71 | # Sphinx documentation 72 | docs/_build/ 73 | 74 | # PyBuilder 75 | .pybuilder/ 76 | target/ 77 | 78 | # Jupyter Notebook 79 | .ipynb_checkpoints 80 | 81 | # IPython 82 | profile_default/ 83 | ipython_config.py 84 | 85 | # pyenv 86 | # For a library or package, you might want to ignore these files since the code is 87 | # intended to run in multiple environments; otherwise, check them in: 88 | # .python-version 89 | 90 | # pipenv 91 | # According to pypa/pipenv#598, it is recommended to include Pipfile.lock in version control. 92 | # However, in case of collaboration, if having platform-specific dependencies or dependencies 93 | # having no cross-platform support, pipenv may install dependencies that don't work, or not 94 | # install all needed dependencies. 95 | #Pipfile.lock 96 | 97 | # poetry 98 | # Similar to Pipfile.lock, it is generally recommended to include poetry.lock in version control. 99 | # This is especially recommended for binary packages to ensure reproducibility, and is more 100 | # commonly ignored for libraries. 101 | # https://python-poetry.org/docs/basic-usage/#commit-your-poetrylock-file-to-version-control 102 | #poetry.lock 103 | 104 | # pdm 105 | # Similar to Pipfile.lock, it is generally recommended to include pdm.lock in version control. 106 | #pdm.lock 107 | # pdm stores project-wide configurations in .pdm.toml, but it is recommended to not include it 108 | # in version control. 109 | # https://pdm.fming.dev/#use-with-ide 110 | .pdm.toml 111 | 112 | # PEP 582; used by e.g. github.com/David-OConnor/pyflow and github.com/pdm-project/pdm 113 | __pypackages__/ 114 | 115 | # Celery stuff 116 | celerybeat-schedule 117 | celerybeat.pid 118 | 119 | # SageMath parsed files 120 | *.sage.py 121 | 122 | # Environments 123 | .env 124 | .venv 125 | env/ 126 | venv/ 127 | ENV/ 128 | env.bak/ 129 | venv.bak/ 130 | 131 | # Spyder project settings 132 | .spyderproject 133 | .spyproject 134 | 135 | # Rope project settings 136 | .ropeproject 137 | 138 | # mkdocs documentation 139 | /site 140 | 141 | # mypy 142 | .mypy_cache/ 143 | .dmypy.json 144 | dmypy.json 145 | 146 | # Pyre type checker 147 | .pyre/ 148 | 149 | # pytype static type analyzer 150 | .pytype/ 151 | 152 | # Cython debug symbols 153 | cython_debug/ 154 | 155 | # PyCharm 156 | # JetBrains specific template is maintained in a separate JetBrains.gitignore that can 157 | # be found at https://github.com/github/gitignore/blob/main/Global/JetBrains.gitignore 158 | # and can be added to the global gitignore or merged into this file. For a more nuclear 159 | # option (not recommended) you can uncomment the following to ignore the entire idea folder. 160 | #.idea/ 161 | .DS_Store 162 | *.ent 163 | notebooks/esm2_t12_35M_UR50D-finetuned-localization/* 164 | *.fasta 165 | *.pdb 166 | *.h5.zip 167 | *.h5 168 | *.fa 169 | *.aln 170 | *.xml -------------------------------------------------------------------------------- /Dockerfile: -------------------------------------------------------------------------------- 1 | # Use the official Python image from the Docker Hub 2 | FROM python:3.11 3 | 4 | # If you have a requirements.txt, copy and install dependencies 5 | COPY requirements.txt . 6 | RUN pip install -r requirements.txt 7 | RUN apt-get update && apt-get install -y wget 8 | # Download and install MUSCLE 9 | RUN wget https://github.com/rcedgar/muscle/releases/download/v5.1/muscle5.1.linux_intel64 -O /usr/local/bin/muscle && \ 10 | chmod +x /usr/local/bin/muscle 11 | 12 | # also in case... 13 | RUN pip install --no-cache-dir jupyterlab 14 | 15 | # Set the working directory 16 | WORKDIR /app 17 | #Include app dir 18 | ENV PYTHONPATH=/app 19 | 20 | # expose port 21 | EXPOSE 8888 22 | 23 | # run jupyter 24 | CMD ["jupyter", "lab", "--ip=0.0.0.0", "--port=8888", "--no-browser", "--allow-root", "--NotebookApp.token=''"] -------------------------------------------------------------------------------- /LICENSE: -------------------------------------------------------------------------------- 1 | Apache License 2 | Version 2.0, January 2004 3 | http://www.apache.org/licenses/ 4 | 5 | TERMS AND CONDITIONS FOR USE, REPRODUCTION, AND DISTRIBUTION 6 | 7 | 1. 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Protein Language Modeling Course

2 | 3 | ![logo_small](https://github.com/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/img/logo_small.gif) 4 | 5 | ---- 6 | 7 | 1. [Topics](topics.md) 8 | 2. [Course Structure](#course-structure) 9 | 3. [References](#references) 10 | 4. [Resources](#other-resources) 11 | 12 | 13 | 14 | ## Course Structure 15 | 16 | | **Theory** | | Link | Data |Models | 17 | |--------------|-------------------------|------------------------------|-----------------|-----------------| 18 | | | [Topics](topics.md) | [slides](slides/intro_pLM.pdf) | | | 19 | | **Hands-on** | | | | | 20 | | | **Sequence Analysis** | [Seq. Analysis Notebook](notebooks/seq_analysis.ipynb) [![Open In Colab](https://colab.research.google.com/assets/colab-badge.svg)](https://colab.research.google.com/github/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/notebooks/seq_analysis.ipynb) | Exploring protein sequence and structure data | | 21 | | | **Fine-tuning a model** | [Model Training Notebook](notebooks/model_training.ipynb) [![Open In Colab](https://colab.research.google.com/assets/colab-badge.svg)](https://colab.research.google.com/github/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/notebooks/model_training.ipynb) | Taking an existing model and tuning it for other prediction/classification tasks | [Evolutionary Scale Modeling (ESM)](https://github.com/facebookresearch/esm) | 22 | | | **Working with Embeddings** | [Embeddings Notebook](notebooks/embeddings.ipynb) [![Open In Colab](https://colab.research.google.com/assets/colab-badge.svg)](https://colab.research.google.com/github/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/notebooks/embeddings.ipynb) | Accessing Protein representations (embeddings) generated by existing LMs | [ProTrans](https://github.com/agemagician/ProtTrans) | 23 | | | **Predictions** | [pML Predictions Notebook](notebooks/prediction.ipynb) [![Open In Colab](https://colab.research.google.com/assets/colab-badge.svg)](https://colab.research.google.com/github/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/notebooks/prediction.ipynb) | Using embeddings for predicting features or classifying sequences | [ProTrans](https://github.com/agemagician/ProtTrans) | 24 | | | **Protein Design** | [Protein Design Notebook](notebooks/prot_design.ipynb)[![Open In Colab](https://colab.research.google.com/assets/colab-badge.svg)](https://colab.research.google.com/github/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/notebooks/prot_design.ipynb) | *De novo* protein design and engineering using a LLM | [ProtGPT2](https://huggingface.co/nferruz/ProtGPT2), [ESM](https://github.com/facebookresearch/esm) | 25 | 26 | #### Working Locally 27 | 28 | 1. Install [Docker](https://docs.docker.com/engine/install/) 29 | 2. From the root of the repository in the terminal run: 30 | ``` 31 | docker compose up --build -d 32 | ``` 33 | 3. Open JupyterLab in any browser via `0.0.0.0:8888` 34 | 35 | To stop run: `docker compose stop` 36 | To stop and remove containers: `docker compose down` 37 | 38 | 39 | #### Working VM 40 | 1. Once you have a VM, download docker in it 41 | - (e.g., [apt install](https://docs.docker.com/engine/install/ubuntu/#install-using-the-repository) via ssh) 42 | - e.g. in VM shell run below 43 | ``` 44 | # Add Docker's official GPG key: 45 | sudo apt-get update 46 | sudo apt-get install ca-certificates curl 47 | sudo install -m 0755 -d /etc/apt/keyrings 48 | sudo curl -fsSL https://download.docker.com/linux/ubuntu/gpg -o /etc/apt/keyrings/docker.asc 49 | sudo chmod a+r /etc/apt/keyrings/docker.asc 50 | 51 | # Add the repository to Apt sources: 52 | echo \ 53 | "deb [arch=$(dpkg --print-architecture) signed-by=/etc/apt/keyrings/docker.asc] https://download.docker.com/linux/ubuntu \ 54 | $(. /etc/os-release && echo "$VERSION_CODENAME") stable" | \ 55 | sudo tee /etc/apt/sources.list.d/docker.list > /dev/null 56 | sudo apt-get update 57 | 58 | sudo apt-get install docker-ce docker-ce-cli containerd.io docker-buildx-plugin docker-compose-plugin 59 | ``` 60 | 2. Clone this repo into the VM or to keep things slim you can move only the below needed files onto VM (e.g., via `scp`) 61 | - notebooks and data folders 62 | - Dockerfile, docker-compose.yml 63 | - requirements.txt 64 | 3. Then run `docker compose up --build -d` 65 | - if you encounter permission denied you may need to run the above command with elevated permissions e.g. `sudo docker compose up --build -d` 66 | - Note: for troubleshooting you can use `docker logs ` e.g., `docker logs jupyter` 67 | 4. The URL to the JupyterLab will be: `:8888` e.g. `12.26.38.408:8888` 68 | - Note: may have to expose port 8888 via the VM's network security group 69 | 5. On your local device, open a browser of your choosing. In the address bar input the URL to JupyterLab. And you should be good to go :) 70 | 6. **Remember to stop the VM container once you are done** 71 | 72 | 73 | ## References 74 | ---- 75 | 1. [Neural Machine Translation by Jointly Learning to Align and Translate](https://arxiv.org/abs/1409.0473) Dzmitry Bahdanau, Kyunghyun Cho, Yoshua Bengio 76 | 77 | 2. [Attention Is All You Need](https://arxiv.org/abs/1706.03762) Ashish Vaswani, Noam Shazeer, Niki Parmar, Jakob Uszkoreit, Llion Jones, Aidan N. Gomez, Lukasz Kaiser, Illia Polosukhin 78 | 79 | 3. [MSA Transformer](https://www.biorxiv.org/content/10.1101/2021.02.12.430858v3) Roshan Rao, Jason Liu, Robert Verkuil, Joshua Meier, John F. Canny, Pieter Abbeel, Tom Sercu, Alexander Rives 80 | 81 | 4. [Transformer-based deep learning for predicting protein properties in the life sciences](https://elifesciences.org/articles/82819) Abel Chandra, Laura Tünnermann, Tommy Löfstedt, Regina Gratz 82 | 83 | 5. [BERTology Meets Biology: Interpreting Attention in Protein Language Models](https://arxiv.org/abs/2006.15222) Jesse Vig, Ali Madani, Lav R. Varshney, Caiming Xiong, Richard Socher, Nazneen Fatema Rajani 84 | 85 | 6. [Broadly applicable and accurate protein design by integrating structure prediction networks and diffusion generative models 86 | ](https://www.biorxiv.org/content/10.1101/2022.12.09.519842v2) Joseph L. Watson, David Juergens, Nathaniel R. Bennett, Brian L. Trippe, Jason Yim, Helen E. Eisenach, Woody Ahern, Andrew J. Borst, Robert J. Ragotte, Lukas F. Milles, Basile I. M. Wicky, Nikita Hanikel, Samuel J. Pellock, Alexis Courbet, William Sheffler, Jue Wang, Preetham Venkatesh, Isaac Sappington, Susana Vázquez Torres, Anna Lauko, Valentin De Bortoli, Emile Mathieu, Regina Barzilay, Tommi S. Jaakkola, Frank DiMaio, Minkyung Baek, David Baker 87 | 88 | 7. [Large language models generate functional protein sequences across diverse families](https://www.nature.com/articles/s41587-022-01618-2) Ali Madani, Ben Krause, Eric R. Greene, Subu Subramanian, Benjamin P. Mohr, James M. Holton, Jose Luis Olmos Jr., Caiming Xiong, Zachary Z. Sun, Richard Socher, James S. Fraser & Nikhil Naik 89 | 90 | 8. [Learning functional properties of proteins with language models](https://www.nature.com/articles/s42256-022-00457-9)Serbulent Unsal, Heval Atas, Muammer Albayrak, Kemal Turhan, Aybar C. Acar & Tunca Doğan 91 | 92 | 9. [Learning the protein language: Evolution, structure, and function](https://www.sciencedirect.com/science/article/pii/S2405471221002039) Tristan Bepler, Bonnie Berger 93 | 94 | 10. [The language of proteins: NLP, machine learning & protein sequences](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050421/) Dan Ofer, Nadav Brandes, Michal Linial 95 | 96 | 11. [Evolutionary-scale prediction of atomic-level protein structure with a language model](https://www.science.org/doi/10.1126/science.ade2574) ZEMING LIN, HALIL AKIN, ROSHAN RAO, BRIAN HIE, ZHONGKAI ZHU, WENTING LU, NIKITA SMETANIN, ROBERT VERKUIL, ORI KABELI, ..., ALEXANDER RIVES 97 | 98 | 12. [Generative power of a protein language model trained on multiple sequence alignments](https://elifesciences.org/articles/79854) Damiano Sgarbossa, Umberto Lupo, Anne-Florence Bitbol 99 | 100 | 13. [How Huge Protein Language Models Could Disrupt Structural Biology](https://towardsdatascience.com/how-huge-protein-language-models-could-disrupt-structural-biology-6b98193f880b) 101 | 102 | 14. [Embeddings from protein language models predict conservation and variant effects](https://link.springer.com/article/10.1007/s00439-021-02411-y) Céline Marquet, Michael Heinzinger, Tobias Olenyi, Christian Dallago, Kyra Erckert, Michael Bernhofer, Dmitrii Nechaev & Burkhard Rost 103 | 104 | 15. [Collectively encoding protein properties enriches protein language models](https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-022-05031-z) Jingmin An & Xiaogang Weng 105 | 106 | 16. [ProGen: Language Modeling for Protein Generation](https://www.biorxiv.org/content/10.1101/2020.03.07.982272v2) Ali Madani, Bryan McCann, Nikhil Naik, Nitish Shirish Keskar, Namrata Anand, Raphael R. Eguchi, Po-Ssu Huang, Richard Socher 107 | 108 | 17. [Transformer protein language models are unsupervised structure learners](https://www.biorxiv.org/content/10.1101/2020.12.15.422761v1) Roshan Rao, Joshua Meier, Tom Sercu, Sergey Ovchinnikov, Alexander Rives 109 | 110 | 18. [Biological structure and function emerge from scaling unsupervised learning to 250 million protein sequences](https://www.pnas.org/doi/full/10.1073/pnas.2016239118) Alexander Rives, Joshua Meier, Tom Sercu and Rob Fergus 111 | 112 | 19. [NetSurfP-3.0: accurate and fast prediction of protein structural features by protein language models and deep learning](https://academic.oup.com/nar/article/50/W1/W510/6596854?) Magnus Haraldson Høie, Erik Nicolas Kiehl, Bent Petersen, Morten Nielsen, Ole Winther, Henrik Nielsen, Jeppe Hallgren, Paolo Marcatili 113 | 114 | 20. [Modeling Protein Using Large-scale Pretrain Language Model](https://arxiv.org/abs/2108.07435) Yijia Xiao, Jiezhong Qiu, Ziang Li, Chang-Yu Hsieh, Jie Tang [github](https://github.com/THUDM/ProteinLM) 115 | 116 | 21. [Deciphering antibody affinity maturation with language models and weakly supervised learning](https://arxiv.org/abs/2112.07782) Jeffrey A. Ruffolo, Jeffrey J. Gray, Jeremias Sulam [github](https://github.com/dohlee/antiberty-pytorch) 117 | 118 | 22. [Protein embeddings improve phage-host interaction prediction](https://www.biorxiv.org/content/10.1101/2023.02.26.530154v1) Mark Edward M. Gonzales, Jennifer C. Ureta, View ORCID ProfileAnish M.S. Shrestha [github](https://github.com/bioinfodlsu/phage-host-prediction) 119 | 120 | 23. [ProteinBERT: a universal deep-learning model of protein sequence and function](https://academic.oup.com/bioinformatics/article/38/8/2102/6502274) Nadav Brandes, Dan Ofer, Yam Peleg, Nadav Rappoport, Michal Linial [github](https://github.com/nadavbra/protein_bert) 121 | 122 | 24. [ProtGPT2 is a deep unsupervised language model for protein design](https://www.nature.com/articles/s41467-022-32007-7) Noelia Ferruz, Steffen Schmidt & Birte Höcker [Hugging Face](https://huggingface.co/nferruz/ProtGPT2?) 123 | 124 | 25. [Protein-Protein Interaction Prediction is Achievable with Large Language Models](https://www.biorxiv.org/content/10.1101/2023.06.07.544109v1.full) Logan Hallee, Jason P. Gleghorn 125 | 126 | 26. [Accurate prediction of virus-host protein-protein interactions via a Siamese neural network using deep protein sequence embeddings](https://www.sciencedirect.com/science/article/pii/S2666389922001568?via%3Dihub) Sumit Madan, Victoria Demina, Marcus Stapf, Oliver Ernst, Holger Fröhlich 127 | 128 | 27. [Structure-informed Language Models Are Protein Designers](https://arxiv.org/abs/2302.01649) Zaixiang Zheng, Yifan Deng, Dongyu Xue, Yi Zhou, Fei YE, Quanquan Gu 129 | 130 | 28. [Graph-BERT and language model-based framework for protein–protein interaction identification](https://www.nature.com/articles/s41598-023-31612-w) Kanchan Jha, Sourav Karmakar & Sriparna Saha 131 | 132 | 29. [Ankh: Optimized Protein Language Model Unlocks General-Purpose Modelling](https://arxiv.org/abs/2301.06568) Ahmed Elnaggar, Hazem Essam, Wafaa Salah-Eldin, Walid Moustafa, Mohamed Elkerdawy, Charlotte Rochereau, Burkhard Rost 133 | 134 | 30. [Contrastive learning in protein language space predicts interactions between drugs and protein targets](https://www.pnas.org/doi/10.1073/pnas.2220778120) Rohit Singh, Samuel Sledzieski, Bryan Bryson, Bonnie Berger 135 | 136 | 31. [De novo design of protein structure and function with RFdiffusion](https://www.nature.com/articles/s41586-023-06415-8) Joseph L. Watson, David Juergens, Nathaniel R. Bennett, Brian L. Trippe, Jason Yim, Helen E. Eisenach, Woody Ahern, Andrew J. Borst, Robert J. Ragotte, Lukas F. Milles, Basile I. M. Wicky, Nikita Hanikel, Samuel J. Pellock, Alexis Courbet, William Sheffler, Jue Wang, Preetham Venkatesh, Isaac Sappington, Susana Vázquez Torres, Anna Lauko, Valentin De Bortoli, Emile Mathieu, Sergey Ovchinnikov, Regina Barzilay, Tommi S. Jaakkola, Frank DiMaio, Minkyung Baek & David Baker 137 | 138 | 32. [Single-sequence protein structure prediction using a language model and deep learning](https://www.nature.com/articles/s41587-022-01432-w) Ratul Chowdhury, Nazim Bouatta, Surojit Biswas, Christina Floristean, Anant Kharkar, Koushik Roy, Charlotte Rochereau, Gustaf Ahdritz, Joanna Zhang, George M. Church, Peter K. Sorger & Mohammed AlQuraishi 139 | 140 | 33. [Before and after AlphaFold2: An overview of protein structure prediction](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011655/) Letícia M. F. Bertoline, Angélica N. Lima, Jose E. Krieger, and Samantha K. Teixeira 141 | 142 | 34. [Evaluating Protein Transfer Learning with TAPE](https://arxiv.org/abs/1906.08230) Roshan Rao, Nicholas Bhattacharya, Neil Thomas, Yan Duan, Xi Chen, John Canny, Pieter Abbeel, Yun S. Song 143 | 144 | 35. [FLIP: Benchmark tasks in fitness landscape inference for proteins](https://www.biorxiv.org/content/10.1101/2021.11.09.467890v2) Christian Dallago, Jody Mou, Kadina E. Johnston, Bruce J. Wittmann, Nicholas Bhattacharya, Samuel Goldman, Ali Madani, Kevin K. Yang 145 | 146 | 36. [Standards, tooling and benchmarks to probe representation learning on proteins](https://openreview.net/forum?id=adODyN-eeJ8) Joaquin Gomez Sanchez, Sebastian Franz, Michael Heinzinger, Burkhard Rost, Christian Dallago 147 | 148 | 37. [Learning meaningful representations of protein sequences](https://www.nature.com/articles/s41467-022-29443-w) Nicki Skafte Detlefsen, Søren Hauberg & Wouter Boomsma 149 | 150 | 38. [Language modelling for biological sequences – curated datasets and baselines](https://www.biorxiv.org/content/10.1101/2020.03.09.983585v1) Jose Juan Almagro Armenteros, Alexander Rosenberg Johansen, Ole Winther, Henrik Nielsen 151 | 152 | 39. [Language models generalize beyond natural proteins](https://www.biorxiv.org/content/10.1101/2022.12.21.521521v1) Robert Verkuil, Ori Kabeli, Yilun Du, Basile I. M. Wicky, Lukas F. Milles, Justas Dauparas, David Baker, Sergey Ovchinnikov, Tom Sercu, Alexander Rives 153 | 154 | 40. [ChemBERTa: Large-Scale Self-Supervised Pretraining for Molecular Property Prediction](https://arxiv.org/abs/2010.09885) Seyone Chithrananda, Gabriel Grand, Bharath Ramsundar 155 | 156 | 41. [SETH predicts nuances of residue disorder from protein embeddings](https://www.frontiersin.org/articles/10.3389/fbinf.2022.1019597/full) Dagmar Ilzhöfer, Michael Heinzinger, Burkhard Rost 157 | 158 | 42. [Exploiting pretrained biochemical language models for targeted drug design](https://academic.oup.com/bioinformatics/article/38/Supplement_2/ii155/6702010) Gökçe Uludoğan, Elif Ozkirimli, Kutlu O Ulgen, Nilgün Karalı, Arzucan Özgür 159 | 160 | 161 | ## Other Resources 162 | ---- 163 | - [Protein Language Workshop](https://github.com/dimiboeckaerts/ProteinLanguageWorkshop) 164 | 165 | - [Awesome protein representation learning](https://github.com/LirongWu/awesome-protein-representation-learning) 166 | 167 | - [Evolutionary Scale Modeling - ESM](https://github.com/facebookresearch/esm) 168 | 169 | - [Huggingface ESM](https://huggingface.co/docs/transformers/model_doc/esm) 170 | 171 | - [Ankh](https://github.com/agemagician/Ankh) 172 | 173 | - [Protein Sequence Embeddings (ProSE)](https://github.com/tbepler/prose) 174 | 175 | - [ProTrans](https://github.com/agemagician/ProtTrans) 176 | 177 | - [ConPlex](https://github.com/samsledje/ConPLex) 178 | 179 | - [Deep Learning with Proteins](https://github.com/huggingface/blog/blob/main/deep-learning-with-proteins.md) 180 | 181 | - [Awesome AI-based for Protein Design](https://github.com/opendilab/awesome-AI-based-protein-design) 182 | 183 | - [Amazon SageMaker Protein Classification](https://github.com/aws-samples/amazon-sagemaker-protein-classification/tree/main) 184 | 185 | - [Huggingface Protein Language Modeling - pytorch](https://github.com/huggingface/notebooks/blob/main/examples/protein_language_modeling.ipynb) 186 | 187 | - [Huggingface Protein Language Modeling - tensorflow](https://github.com/huggingface/notebooks/blob/main/examples/protein_language_modeling-tf.ipynb) 188 | 189 | - [Building a Text Generation Model from Scratch](https://wingedsheep.com/building-a-language-model/) 190 | 191 | - [Training the Transformer Model](https://machinelearningmastery.com/training-the-transformer-model/) 192 | 193 | - [GearNet: Geometry-Aware Relational Graph Neural Network](https://github.com/DeepGraphLearning/GearNet) 194 | 195 | - [UniLanguage](https://github.com/alrojo/UniLanguage) 196 | 197 | - [SETH](https://github.com/DagmarIlz/SETH) 198 | 199 | 200 | -------------------------------------------------------------------------------- /data/Test_seed1.fasta: -------------------------------------------------------------------------------- 1 | >Test_1 2 | MIQEKDKYVVASVTILESNQILDKGSIQTSGIELNYYMKYQKY 3 | >Test_2 4 | MIQEKDKYVVASVTILESNQLLKEANSSGN 5 | >Test_3 6 | MIQEKDKYVVASVTILESNQNSDVFIDLTNLTVEHKKLLN 7 | >Test_4 8 | MIQEKDKYVVASVTILESNQVFDAMGFGGFLNINRKKFYNDL 9 | >Test_5 10 | MIQEKDKYVVASVTILESNQVFFDSPEIKKLGLVTLKAKYD 11 | >Test_6 12 | MIQEKDKYVVASVTILESNQFGMKRNILYKETKALRAK 13 | >Test_7 14 | MIQEKDKYVVASVTILESNQHGNIQIAQIQIFTNSKEPTVFD 15 | >Test_8 16 | MIQEKDKYVVASVTILESNQWFHENICLAGLWHVGKCKS 17 | >Test_9 18 | MIQEKDKYVVASVTILESNQIYISEYLLIELKEYVLNIISETL 19 | >Test_10 20 | MIQEKDKYVVASVTILESNQSLGQIIQRAIDFSDNNTNLRSIDG 21 | >Test_11 22 | MIQEKDKYVVASVTILESNQCILGSVELAIDVTEQERLSRELEQV 23 | >Test_12 24 | MIQEKDKYVVASVTILESNQVGKAFIENYLRDNKY 25 | >Test_13 26 | MIQEKDKYVVASVTILESNQMGGYVATGHGNFISPVY 27 | >Test_14 28 | MIQEKDKYVVASVTILESNQATVTLRTKATYRNLSRKWTLFG 29 | >Test_15 30 | MIQEKDKYVVASVTILESNQFEGNMIQIYYESTHSPT 31 | >Test_16 32 | MIQEKDKYVVASVTILESNQLLLTYNVTSLTQNQQPWGS 33 | >Test_17 34 | MIQEKDKYVVASVTILESNQKKQKEYKIKRVLKYEGNS 35 | >Test_18 36 | MIQEKDKYVVASVTILESNQIYTFESNKDYMITIALRE 37 | >Test_19 38 | MIQEKDKYVVASVTILESNQALFLLTVMESQLQNEKSGKALNRMRE 39 | >Test_20 40 | MIQEKDKYVVASVTILESNQWTGNIQNYKQTAEAILTD 41 | -------------------------------------------------------------------------------- /data/Test_seed1_aligned.aln: -------------------------------------------------------------------------------- 1 | >Test_5 2 | MIQEKDKYVVASVTILESNQV-----FFDSPEIKKLGLVTLKAKYD---- 3 | >Test_7 4 | MIQEKDKYVVASVTILESNQH---GNIQIAQIQIFTNSKEPTVFD----- 5 | >Test_1 6 | MIQEKDKYVVASVTILESNQI---LDKGSIQTSGIELNYYMKYQKY---- 7 | >Test_9 8 | MIQEKDKYVVASVTILESNQIYISEYLLIELKEYVLNIISETL------- 9 | >Test_10 10 | MIQEKDKYVVASVTILESNQS-----LGQIIQRAIDFSDNNTNLRSIDG- 11 | >Test_11 12 | MIQEKDKYVVASVTILESNQC-----ILGSVELAIDVTEQERLSRELEQV 13 | >Test_19 14 | MIQEKDKYVVASVTILESNQA---LFLLTVMESQLQNEKSGKALNRMRE- 15 | >Test_8 16 | MIQEKDKYVVASVTILESNQW-------FHENICLAGLWHVGKCKS---- 17 | >Test_3 18 | MIQEKDKYVVASVTILESNQN-----SDVFIDLTNLTVEHKKLLN----- 19 | >Test_14 20 | MIQEKDKYVVASVTILESNQA----TVTLRTKATYRNLSRKWTLFG---- 21 | >Test_4 22 | MIQEKDKYVVASVTILESNQVFDAMGFGGFLNINRKKFYNDL-------- 23 | >Test_18 24 | MIQEKDKYVVASVTILESNQI-----YTFESNKDYMITIALRE------- 25 | >Test_17 26 | MIQEKDKYVVASVTILESNQK------KQKEYKIKRVLKYEGNS------ 27 | >Test_16 28 | MIQEKDKYVVASVTILESNQL-----LLTYNVTSLTQNQQPWGS------ 29 | >Test_12 30 | MIQEKDKYVVASVTILESNQV-----GKAFIENYLRDNKY---------- 31 | >Test_6 32 | MIQEKDKYVVASVTILESNQF------GMKRNILYKETKALRAK------ 33 | >Test_20 34 | MIQEKDKYVVASVTILESNQW------TGNIQNYKQTAEAILTD------ 35 | >Test_13 36 | MIQEKDKYVVASVTILESNQM------GGYVATGHGNFISPVY------- 37 | >Test_15 38 | MIQEKDKYVVASVTILESNQF-----EGNMIQIYYESTHSPT-------- 39 | >Test_2 40 | MIQEKDKYVVASVTILESNQL-------------LKEANSSGN------- 41 | -------------------------------------------------------------------------------- /data/per_protein_embeddings.h5.zip: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/data/per_protein_embeddings.h5.zip -------------------------------------------------------------------------------- /docker-compose.yml: -------------------------------------------------------------------------------- 1 | services: 2 | jupyter: 3 | container_name: jupyter 4 | build: 5 | context: ${DOCKER_VOLUME_DIRECTORY:-.} 6 | dockerfile: ${DOCKER_VOLUME_DIRECTORY:-.}/Dockerfile 7 | ports: 8 | - "8888:8888" 9 | volumes: 10 | - ${DOCKER_VOLUME_DIRECTORY:-.}/notebooks:/app 11 | - ${DOCKER_VOLUME_DIRECTORY:-.}/data:/app/data -------------------------------------------------------------------------------- /img/fine-tuning.png: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/img/fine-tuning.png -------------------------------------------------------------------------------- /img/gpu.png: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/img/gpu.png -------------------------------------------------------------------------------- /img/logo_small.gif: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/img/logo_small.gif -------------------------------------------------------------------------------- /img/nb_logo.png: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/img/nb_logo.png -------------------------------------------------------------------------------- /img/protgpt2.png: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/img/protgpt2.png -------------------------------------------------------------------------------- /notebooks/embeddings.ipynb: -------------------------------------------------------------------------------- 1 | { 2 | "cells": [ 3 | { 4 | "cell_type": "markdown", 5 | "id": "06460c02-2004-436b-aa38-1ae0a7587052", 6 | "metadata": {}, 7 | "source": [ 8 | "" 9 | ] 10 | }, 11 | { 12 | "cell_type": "markdown", 13 | "id": "8bf874eb-8949-41dd-a33b-0e55ba2954c6", 14 | "metadata": {}, 15 | "source": [ 16 | "[![Open In Colab](https://colab.research.google.com/assets/colab-badge.svg)](https://colab.research.google.com/github/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/notebooks/embeddings.ipynb)\n", 17 | "\n", 18 | "\n", 19 | "This is a version of the notebook from [SETH](https://github.com/DagmarIlz/SETH) --- [here](https://colab.research.google.com/drive/1vDWh5YI_BPxQg0ku6CxKtSXEJ25u2wSq?usp=sharing)." 20 | ] 21 | }, 22 | { 23 | "cell_type": "code", 24 | "execution_count": null, 25 | "id": "cd6f0c8f-d9db-4623-a2ee-483008dc9d74", 26 | "metadata": {}, 27 | "outputs": [], 28 | "source": [ 29 | "# uncomment the below to install dependencies for colab\n", 30 | "#!pip install \"transformers[torch]\" sentencepiece h5py biopython > /dev/null" 31 | ] 32 | }, 33 | { 34 | "cell_type": "markdown", 35 | "id": "4efcc6ce-9843-4541-a6de-6b3a6ba14c45", 36 | "metadata": {}, 37 | "source": [ 38 | "

Important

\n", 39 | "If you are running in Google Colab, change the Notebook settings to use `GPU`.\n", 40 | "\n", 41 | "Just follow **Edit** > **Notebook settings** or **Runtime** > **Change runtime type** and select **GPU** as Hardware accelerator.\n", 42 | "\n", 43 | "![gpu.png](../img/gpu.png)\n" 44 | ] 45 | }, 46 | { 47 | "cell_type": "markdown", 48 | "id": "75061fa6-eea7-42dc-b057-5da1c56094c0", 49 | "metadata": { 50 | "id": "5c0749e1" 51 | }, 52 | "source": [ 53 | "# Embedding Protein Sequences\n", 54 | "\n", 55 | "In this notebook, we will use a pre-trained language model, [ProtT5-XL-UniRef50](https://huggingface.co/Rostlab/prot_t5_xl_uniref50), to encode the protein sequences of 5000+ $\\beta$-$lactamase$ TEM-type varients from FASTA file [P62593.fasta](https://github.com/facebookresearch/esm/blob/2b369911bb5b4b0dda914521b9475cad1656b2ac/examples/data/P62593.fasta). This data was subsetted from a deep mutational scan released by [Gray et al. (2018)](https://www.cell.com/cell-systems/pdfExtended/S2405-4712(17)30492-1). \n", 56 | "\n", 57 | "The goal of this notebook is to obtain an embedding (fixed-dimensional vector representation) for each mutated sequence.\n", 58 | "\n", 59 | "Although the embedding won't capture all the information from the original data, good embedding representations allow us to analyze, cluster, or use them as features to train machine learning models. \n", 60 | "\n", 61 | "The embeddings generated in this notebook will then be used in the next exercise (prediction.ipynb) to train a simple varient predictor (i.e., predict the activity of the protein mutation)." 62 | ] 63 | }, 64 | { 65 | "cell_type": "markdown", 66 | "id": "38b6f6b9-0778-4435-a515-e9616522c4b3", 67 | "metadata": {}, 68 | "source": [ 69 | "
\n", 70 | "\n", 71 | "

NOTE

\n", 72 | "

\n", 73 | " Even when using GPU, embedding the protein sequences takes some time (~25mins) so to begin go ahead and run all cells of this notebook so that the process is started in the background as we review the notebook.\n", 74 | "

\n", 75 | "

\n", 76 | " A shortcut to running all cells is going to the \"Runtime\" menu and selecting \"Run all\".\n", 77 | "\n", 78 | "\n", 79 | "

" 80 | ] 81 | }, 82 | { 83 | "cell_type": "markdown", 84 | "id": "0e5c4fc2-00ea-4e24-90fa-d96bf3751810", 85 | "metadata": { 86 | "id": "5c0749e1" 87 | }, 88 | "source": [ 89 | "----\n", 90 | "\n", 91 | "## The Data: P62593 Sequences\n", 92 | "\n", 93 | "To start we will import and explore the dataset: " 94 | ] 95 | }, 96 | { 97 | "cell_type": "code", 98 | "execution_count": null, 99 | "id": "e520014b-391d-41b0-ad62-7d51f56511b8", 100 | "metadata": {}, 101 | "outputs": [], 102 | "source": [ 103 | "# Set up working directories and download files/checkpoints \n", 104 | "!mkdir protT5 # directory for storing checkpoints, results etc\n", 105 | "!mkdir protT5/output # directory for storing your embeddings\n", 106 | "!curl -o P62593.fasta https://dl.fbaipublicfiles.com/fair-esm/examples/P62593.fasta" 107 | ] 108 | }, 109 | { 110 | "cell_type": "code", 111 | "execution_count": null, 112 | "id": "bcfc1b48-24d6-4d6f-86aa-9d3048a6d1d0", 113 | "metadata": {}, 114 | "outputs": [], 115 | "source": [ 116 | "# Import dependencies\n", 117 | "from transformers import T5EncoderModel, T5Tokenizer\n", 118 | "import torch\n", 119 | "import h5py\n", 120 | "import time\n", 121 | "from Bio import SeqIO\n", 122 | "\n", 123 | "# Path variables\n", 124 | "per_protein_path = \"./protT5/output/per_protein_embeddings.h5\" # where to store the embeddings\n", 125 | "seq_path = 'P62593.fasta' # where the fasta file is saved\n", 126 | "\n", 127 | "# check whether GPU is available\n", 128 | "device = torch.device('cuda:0' if torch.cuda.is_available() else 'cpu')\n", 129 | "print(f\"Using {device}\")" 130 | ] 131 | }, 132 | { 133 | "cell_type": "code", 134 | "execution_count": null, 135 | "id": "009ac9f9-b169-4696-abf6-a1c0a3ef8edf", 136 | "metadata": {}, 137 | "outputs": [], 138 | "source": [ 139 | "def read_fasta(fasta_path:str) -> dict:\n", 140 | " '''\n", 141 | " reads in fasta file and returns a dictionary with primary id/sequence key/value pairs \n", 142 | " '''\n", 143 | " \n", 144 | " # dictionary to append to\n", 145 | " seqs = {}\n", 146 | " \n", 147 | " # read in and parse fasta file\n", 148 | " with open(fasta_path) as handle:\n", 149 | " for record in SeqIO.parse(handle, \"fasta\"):\n", 150 | " # append each varient to the dict\n", 151 | " seqs[record.id] = record.seq\n", 152 | "\n", 153 | " # verbose\n", 154 | " example_id=next(iter(seqs))\n", 155 | " print(f\"Read {len(seqs)} sequences.\")\n", 156 | " print(f\"Example:\\nKey: {example_id}\\nValue: {seqs[example_id]}\")\n", 157 | "\n", 158 | " return seqs" 159 | ] 160 | }, 161 | { 162 | "cell_type": "code", 163 | "execution_count": null, 164 | "id": "3aa98336-a298-4f5f-87b6-98718ec5e22f", 165 | "metadata": {}, 166 | "outputs": [], 167 | "source": [ 168 | "# read in file\n", 169 | "fasta_output = read_fasta(seq_path)" 170 | ] 171 | }, 172 | { 173 | "cell_type": "markdown", 174 | "id": "717503ab-a593-4af2-8128-4e64491c3ebc", 175 | "metadata": {}, 176 | "source": [ 177 | "In the FASTA file there are 5,397 sequences. As we can see in the example above from our fasta dictionary, each entry contains:\n", 178 | "\n", 179 | "- key: `{index}|beta-lactamase_{mutation}|{scaled_varient_effect}`\n", 180 | " > in prediction.ipynb we will be predicting the `scaled_varient_effect` value, which describes the scaled effect of the mutation. \n", 181 | "- value: the mutated $\\beta$-lactamase sequence, where a single residue is mutated (swapped with another amino acid)" 182 | ] 183 | }, 184 | { 185 | "cell_type": "markdown", 186 | "id": "ef06a40d-a52f-46bf-bfe7-3b2374eea224", 187 | "metadata": {}, 188 | "source": [ 189 | "## The Model: ProtT5-XL-UniRef50\n", 190 | "\n", 191 | "ProtT5-XL-UniRef50 is based on the t5-3b model and was pretrained on a large corpus of protein sequences in a self-supervised fashion. This means it was pretrained on the raw protein sequences only, with **no humans-in-the-loop labelling** them in any way (which is why it can use lots of publicly available data) with an automatic process to generate inputs and labels from those protein sequences.\n", 192 | "\n", 193 | "This model only contains the encoder portion of the original ProtT5-XL-UniRef50 model using half precision (float16). As such, this model can efficiently be used to create protein/ amino acid representations. When used for training downstream networks/ feature extraction, these embeddings produced the same performance (established empirically by comparing on several downstream tasks). \n", 194 | "\n", 195 | "In the following cells we will prepare functions that will later assist us when generating the embeddings. " 196 | ] 197 | }, 198 | { 199 | "cell_type": "markdown", 200 | "id": "d072fe5a-3d34-475b-b025-abb7f3eef1f8", 201 | "metadata": {}, 202 | "source": [ 203 | "### `get_T5_model()` Load encoder-part of ProtT5 in half-precision\n", 204 | "\n", 205 | "To start we create a function that will load the model and associated tokenizer. Recall from the previous notebook (model_training.ipynb) where every model on `transformers` comes with an associated `tokenizer` that handles tokenization for it, where tokenization for protein language models involve coverting each amino acid to a single token.\n", 206 | "\n", 207 | "**Recall: Fine-tuning flow chart from the previous notebook**\n", 208 | "![Chart of the pretrained model fine-tuning process](../img/fine-tuning.png)\n", 209 | "\n", 210 | "\n", 211 | "This function accomplishes the \"Model Checkpoint Loading\" step. " 212 | ] 213 | }, 214 | { 215 | "cell_type": "code", 216 | "execution_count": null, 217 | "id": "ac1c2e47-9131-41f6-b39b-2da11b4afe2f", 218 | "metadata": {}, 219 | "outputs": [], 220 | "source": [ 221 | "# Load ProtT5 in half-precision (more specifically: the encoder-part of ProtT5-XL-U50) \n", 222 | "def get_T5_model():\n", 223 | " '''\n", 224 | " retrieves the model and tokenizer\n", 225 | " '''\n", 226 | " # specify the encorder-part of the model \n", 227 | " model_checkpoint = 'Rostlab/prot_t5_xl_half_uniref50-enc'\n", 228 | " \n", 229 | " # import the model \n", 230 | " model = T5EncoderModel.from_pretrained(model_checkpoint)\n", 231 | " \n", 232 | " model = model.to(device) # move model to GPU\n", 233 | " model = model.eval() # set model to evaluation model\n", 234 | " \n", 235 | " # import tokenizer\n", 236 | " tokenizer = T5Tokenizer.from_pretrained(model_checkpoint)\n", 237 | "\n", 238 | " return model, tokenizer" 239 | ] 240 | }, 241 | { 242 | "cell_type": "markdown", 243 | "id": "4404313f-0c46-4cae-acea-5bfdbe86bd99", 244 | "metadata": {}, 245 | "source": [ 246 | "Let's use the function:" 247 | ] 248 | }, 249 | { 250 | "cell_type": "code", 251 | "execution_count": null, 252 | "id": "5282b4cc-36f4-4c70-93f2-5fb32a67f6b9", 253 | "metadata": {}, 254 | "outputs": [], 255 | "source": [ 256 | "# loading model\n", 257 | "model, tokenizer = get_T5_model()" 258 | ] 259 | }, 260 | { 261 | "cell_type": "markdown", 262 | "id": "6ef88997-d8c8-4c62-b394-1d2c3b005a4f", 263 | "metadata": {}, 264 | "source": [ 265 | "### `get_embeddings()` Using the model to generate the embeddings\n", 266 | "\n", 267 | "From the flow chart above, the function `get_embeddings()` includes the 'Tokenization' and 'Dataset Creation' steps. Additionally, the model will encode the sequences. " 268 | ] 269 | }, 270 | { 271 | "cell_type": "code", 272 | "execution_count": null, 273 | "id": "261698df-2497-4f6d-89ef-1df09736110a", 274 | "metadata": {}, 275 | "outputs": [], 276 | "source": [ 277 | "def get_embeddings(model, tokenizer, seqs, max_seq_len=1000, max_batch=100):\n", 278 | " '''\n", 279 | " use the encoder to embbed the sequences via batch-processing\n", 280 | " -----\n", 281 | " \n", 282 | " parameters:\n", 283 | " model: from get_T5_model()\n", 284 | " tokenizer: from get_T5_model()\n", 285 | " seqs: the dictionary of sequences generated by read_fasta() \n", 286 | " max_seq_length: the upper sequences length for applying batch-processing\n", 287 | " max_batch: the upper number of sequences per batch\n", 288 | " \n", 289 | " returns:\n", 290 | " results: a dictionary containing the embedding representations of the sequences\n", 291 | " '''\n", 292 | "\n", 293 | " # initialize a dictionary, the embeddings will be accessible from results['protein_embs'] \n", 294 | " results = {\"protein_embs\" : dict()}\n", 295 | "\n", 296 | " # sort sequences according to length (reduces unnecessary padding --> speeds up embedding)\n", 297 | " seq_dict = sorted(seqs.items(), \n", 298 | " # 'key' option is a function that serves as a basis of sort comparison.\n", 299 | " key=lambda kv: len(seqs[kv[0]]), \n", 300 | " # sort by descending order\n", 301 | " reverse=True\n", 302 | " )\n", 303 | " \n", 304 | " # for time tracking\n", 305 | " start = time.time()\n", 306 | " \n", 307 | " # initialize empty list\n", 308 | " batch = list()\n", 309 | " \n", 310 | " # for each item in the dictionary\n", 311 | " for seq_idx, (pdb_id, seq) in enumerate(seq_dict, 1):\n", 312 | " \n", 313 | " # add space between residues\n", 314 | " seq = ' '.join(list(seq))\n", 315 | " \n", 316 | " # length of sequence with spaces\n", 317 | " seq_len = len(seq)\n", 318 | " \n", 319 | " # append to batch list as tuple\n", 320 | " batch.append((pdb_id, seq, seq_len))\n", 321 | "\n", 322 | " # creates n-tuple pairs from each element in batch\n", 323 | " pdb_ids, seqs, seq_lens = zip(*batch)\n", 324 | " \n", 325 | " # empty list\n", 326 | " batch = list()\n", 327 | " \n", 328 | " # Data Preparation and Tokenization:\n", 329 | "\n", 330 | " # add_special_tokens adds extra token at the end of each sequence\n", 331 | " token_encoding = tokenizer.batch_encode_plus(seqs, add_special_tokens=True, padding=\"longest\")\n", 332 | " \n", 333 | " # making the tokenized sequence into a tensor\n", 334 | " input_ids = torch.tensor(token_encoding['input_ids']).to(device)\n", 335 | " \n", 336 | " # now making the mask into a tensor\n", 337 | " attention_mask = torch.tensor(token_encoding['attention_mask']).to(device)\n", 338 | " \n", 339 | " # Generate Embedding:\n", 340 | " \n", 341 | " # using the model to encode the sequence, generating an embedding representation\n", 342 | " try:\n", 343 | " with torch.no_grad():\n", 344 | " embedding_repr = model(input_ids, attention_mask=attention_mask)\n", 345 | " # verbosity for progress tracking\n", 346 | " print(f'Currently, embedding {pdb_id}')\n", 347 | " except RuntimeError:\n", 348 | " print(\"RuntimeError during embedding for {} (L={})\".format(pdb_id, seq_len))\n", 349 | " continue\n", 350 | " \n", 351 | " # Putting together the dataset:\n", 352 | " \n", 353 | " # slice off padding if any \n", 354 | " emb = embedding_repr.last_hidden_state[0,:seq_len]\n", 355 | "\n", 356 | " # average along column\n", 357 | " protein_emb = emb.mean(dim=0)\n", 358 | "\n", 359 | " # save the embedding into results dictionary where the key = the fasta file entry header\n", 360 | " results[\"protein_embs\"][pdb_id] = protein_emb.detach().cpu().numpy().squeeze()\n", 361 | "\n", 362 | " # get time elapsed\n", 363 | " passed_time=time.time()-start\n", 364 | " avg_time = passed_time/len(results[\"protein_embs\"])\n", 365 | " \n", 366 | " # final verbose\n", 367 | " print('\\n############# EMBEDDING STATS #############')\n", 368 | " print('Total number of per-protein embeddings: {}'.format(len(results[\"protein_embs\"])))\n", 369 | " print(\"Time for generating embeddings: {:.1f}[m] ({:.3f}[s/protein])\".format(\n", 370 | " passed_time/60, avg_time ))\n", 371 | " print('\\n############# END #############')\n", 372 | " \n", 373 | " return results" 374 | ] 375 | }, 376 | { 377 | "cell_type": "markdown", 378 | "id": "53ccafd2-6032-4e50-be6a-53e98897f922", 379 | "metadata": {}, 380 | "source": [ 381 | "**NOTE: What are special tokens?** \n", 382 | "\n", 383 | "Special tokens aren't present in the input text, but carry important meaning that we want the model to act on. For exmaple (not spevific to our model): \n", 384 | "- [PAD] Padding token — Added to the end of shorter inputs so that all inputs have the same length. This is because inputs to a neural network model are typically batched and the model operates on entire batches. \n", 385 | "- [UNK] Unknown token — Used to limit the number of distinct tokens. For example, if we want a vocabulary of at most 1000 tokens but the input text has 1200, then the remaining 200 will be converted to [UNK].\n", 386 | " \n", 387 | "You can read more [here](https://medium.com/@alexkubiesa/special-tokens-in-tensorflow-3c7718dcb0ef).\n", 388 | "\n", 389 | "We will move on and use the function to get the embeddings:" 390 | ] 391 | }, 392 | { 393 | "cell_type": "code", 394 | "execution_count": null, 395 | "id": "6f4097b1-8da4-4cd7-9be1-4caf817294ab", 396 | "metadata": {}, 397 | "outputs": [], 398 | "source": [ 399 | "# Compute embeddings\n", 400 | "results = get_embeddings(model, tokenizer, fasta_output)" 401 | ] 402 | }, 403 | { 404 | "cell_type": "markdown", 405 | "id": "fc2e3350-2791-4773-99f2-e55113f288ea", 406 | "metadata": {}, 407 | "source": [ 408 | "### `save_embeddings()` Writing the embeddings to a file\n", 409 | "\n", 410 | "For our final function, we will write the embeddings to a file. We will load this file into prediction.ipynb to train machine learning models. This is also a copy of the embedding file in the reposition in _data/_. " 411 | ] 412 | }, 413 | { 414 | "cell_type": "code", 415 | "execution_count": null, 416 | "id": "6986186f-93f3-4efe-9597-3c60ce5059a5", 417 | "metadata": {}, 418 | "outputs": [], 419 | "source": [ 420 | "def save_embeddings(emb_dict:dict , out_path:str):\n", 421 | " '''\n", 422 | " takes the resulting embeddings from get_embeddings() and saves to a compressed h5 file\n", 423 | " -----\n", 424 | " \n", 425 | " parameters:\n", 426 | " emb_dict (dict): dictionary that is in results['protein_embs'] \n", 427 | " out_path (str): path and filename where the embeddings will be saved\n", 428 | " '''\n", 429 | " \n", 430 | " with h5py.File(str(out_path), \"w\") as hf:\n", 431 | " for sequence_id, embedding in emb_dict.items():\n", 432 | " hf.create_dataset(sequence_id, data=embedding)\n", 433 | " \n", 434 | " return None" 435 | ] 436 | }, 437 | { 438 | "cell_type": "code", 439 | "execution_count": null, 440 | "id": "aea3a1d4-0091-4134-9773-0a901f644a12", 441 | "metadata": {}, 442 | "outputs": [], 443 | "source": [ 444 | "# write embeddings to file\n", 445 | "save_embeddings(results[\"protein_embs\"], per_protein_path)" 446 | ] 447 | } 448 | ], 449 | "metadata": { 450 | "kernelspec": { 451 | "display_name": "Python 3 (ipykernel)", 452 | "language": "python", 453 | "name": "python3" 454 | }, 455 | "language_info": { 456 | "codemirror_mode": { 457 | "name": "ipython", 458 | "version": 3 459 | }, 460 | "file_extension": ".py", 461 | "mimetype": "text/x-python", 462 | "name": "python", 463 | "nbconvert_exporter": "python", 464 | "pygments_lexer": "ipython3", 465 | "version": "3.10.9" 466 | } 467 | }, 468 | "nbformat": 4, 469 | "nbformat_minor": 5 470 | } 471 | -------------------------------------------------------------------------------- /notebooks/model_training.ipynb: -------------------------------------------------------------------------------- 1 | { 2 | "cells": [ 3 | { 4 | "cell_type": "markdown", 5 | "id": "3494f2e1-0e62-4d3d-a161-6cff27727f78", 6 | "metadata": {}, 7 | "source": [ 8 | "" 9 | ] 10 | }, 11 | { 12 | "cell_type": "markdown", 13 | "id": "d183c1c8-5e35-4eec-9078-caccab5c4708", 14 | "metadata": {}, 15 | "source": [ 16 | "[![Open In Colab](https://colab.research.google.com/assets/colab-badge.svg)](https://colab.research.google.com/github/Multiomics-Analytics-Group/course_protein_language_modeling/blob/main/notebooks/model_training.ipynb)\n", 17 | "\n", 18 | "\n", 19 | "This is a version of the notebook from [Matthew Carrigan](https://huggingface.co/Rocketknight1) --- [here](https://huggingface.co/blog/deep-learning-with-proteins)." 20 | ] 21 | }, 22 | { 23 | "cell_type": "code", 24 | "execution_count": 1, 25 | "id": "a78e617c-c8a7-4715-88d4-06e31e947c4a", 26 | "metadata": {}, 27 | "outputs": [], 28 | "source": [ 29 | "# uncomment the below to install dependencies for colab\n", 30 | "#!pip install \"transformers[torch]\" datasets evaluate biopython" 31 | ] 32 | }, 33 | { 34 | "attachments": {}, 35 | "cell_type": "markdown", 36 | "id": "5a6eb017-b2dc-4dbe-8771-69f1443d89e3", 37 | "metadata": {}, 38 | "source": [ 39 | "

Important

\n", 40 | "If you are running in Google Colab, change the Notebook settings to use `GPU`.\n", 41 | "\n", 42 | "Just follow **Edit** > **Notebook settings** or **Runtime** > **Change runtime type** and select **GPU** as Hardware accelerator.\n", 43 | "\n", 44 | "\n" 45 | ] 46 | }, 47 | { 48 | "cell_type": "markdown", 49 | "id": "85f3e1b8-5517-4016-b7db-f1bb3bb33d31", 50 | "metadata": { 51 | "id": "5c0749e1" 52 | }, 53 | "source": [ 54 | "# Fine-Tuning Protein Language Models" 55 | ] 56 | }, 57 | { 58 | "cell_type": "markdown", 59 | "id": "1b38b001-2450-4792-8647-31bae0bca58e", 60 | "metadata": { 61 | "id": "1d81db83" 62 | }, 63 | "source": [ 64 | "In this notebook, we are going to use transfer learning to fine-tune a large, pre-trained protein language model to predict **Subcellular location** based on protein sequence. \n", 65 | "\n", 66 | "The specific model we are going to use is [ESM](https://github.com/facebookresearch/esm), which is the state-of-the-art protein language model at the time of writing (November 2022) and described in detail in [Lin et al, 2022](https://www.biorxiv.org/content/10.1101/2022.07.20.500902v1).\n", 67 | "\n", 68 | "There are several ESM-2 checkpoints with differing model sizes. **A checkpoint** is an intermediate dump of a model’s entire internal state (weights, learning rate, etc.) so that the framework can resume the training from this point whenever desired. \n", 69 | "\n", 70 | "Larger models will generally have better accuracy, but they require more GPU memory and will take much longer to train. The available ESM-2 checkpoints are:\n", 71 | "\n", 72 | "| Checkpoint name | Num layers | Num parameters |\n", 73 | "|------------------------------|----|----------|\n", 74 | "| `esm2_t48_15B_UR50D` | 48 | 15B |\n", 75 | "| `esm2_t36_3B_UR50D` | 36 | 3B |\n", 76 | "| `esm2_t33_650M_UR50D` | 33 | 650M |\n", 77 | "| `esm2_t30_150M_UR50D` | 30 | 150M |\n", 78 | "| `esm2_t12_35M_UR50D` | 12 | 35M |\n", 79 | "| `esm2_t6_8M_UR50D` | 6 | 8M |\n", 80 | "\n", 81 | "*Note*: larger checkpoints may be very difficult to train without a large cloud GPU like an A100 or H100, and the largest 15B parameter checkpoint will probably be impossible to train on **any** single GPU! Also, note that memory usage for attention during training will scale as `O(batch_size * num_layers * seq_len^2)`, so larger models on long sequences will use quite a lot of memory! We will use the `esm2_t12_35M_UR50D` checkpoint for this notebook, which should train on any Colab instance or modern GPU." 82 | ] 83 | }, 84 | { 85 | "cell_type": "code", 86 | "execution_count": 2, 87 | "id": "2c447d8c-00ee-4a3b-b924-ccc36e865828", 88 | "metadata": { 89 | "id": "32e605a2" 90 | }, 91 | "outputs": [], 92 | "source": [ 93 | "model_checkpoint = \"facebook/esm2_t12_35M_UR50D\"" 94 | ] 95 | }, 96 | { 97 | "attachments": {}, 98 | "cell_type": "markdown", 99 | "id": "2cbf0310-6664-4938-80cf-0d6cbe741f2e", 100 | "metadata": { 101 | "id": "a8e6ac19" 102 | }, 103 | "source": [ 104 | "# Fine-tuning\n", 105 | "\n", 106 | "" 107 | ] 108 | }, 109 | { 110 | "cell_type": "markdown", 111 | "id": "a7f033aa-d819-4e16-86de-feecf3d7b17c", 112 | "metadata": {}, 113 | "source": [ 114 | "## Subcellular Location" 115 | ] 116 | }, 117 | { 118 | "cell_type": "markdown", 119 | "id": "33d88492-5d1e-4f4a-b09d-0f0642f17105", 120 | "metadata": { 121 | "id": "c5bc122f" 122 | }, 123 | "source": [ 124 | "## Data Collection" 125 | ] 126 | }, 127 | { 128 | "cell_type": "markdown", 129 | "id": "57191840-da48-42ae-a5b9-c2eb87d0835f", 130 | "metadata": { 131 | "id": "4c91d394" 132 | }, 133 | "source": [ 134 | "We will gather data from [UniProt](https://www.uniprot.org/) to create a pair of lists: `sequences` and `labels`. `sequences` will be a list of protein sequences and `labels` will be a list of the category for each sequence (integers)." 135 | ] 136 | }, 137 | { 138 | "cell_type": "code", 139 | "execution_count": 3, 140 | "id": "410bc787-ca60-44f5-98e6-1cb23e7e5088", 141 | "metadata": { 142 | "id": "c718ffbc" 143 | }, 144 | "outputs": [ 145 | { 146 | "name": "stdout", 147 | "output_type": "stream", 148 | "text": [ 149 | "https://rest.uniprot.org/uniprotkb/stream?compressed=true&fields=accession%2Csequence%2Ccc_subcellular_location&format=tsv&query=%28%28organism_id%3A9606%29+AND+%28reviewed%3Atrue%29+AND+%28length%3A%5B80+TO+500%5D%29%29\n" 150 | ] 151 | } 152 | ], 153 | "source": [ 154 | "import requests\n", 155 | "import urllib.parse\n", 156 | "\n", 157 | "organism = 9606\n", 158 | "fields = \",\".join(['accession', 'sequence', 'cc_subcellular_location'])\n", 159 | "query = f'((organism_id:{organism}) AND (reviewed:true) AND (length:[80 TO 500]))'\n", 160 | "params = {\n", 161 | " 'compressed': 'true', \n", 162 | " 'fields': fields, \n", 163 | " 'format':'tsv', \n", 164 | " 'query':query\n", 165 | "}\n", 166 | "query_url = 'https://rest.uniprot.org/uniprotkb/stream?'\n", 167 | "query_url += urllib.parse.urlencode(params)\n", 168 | "\n", 169 | "# take a look \n", 170 | "print(query_url)" 171 | ] 172 | }, 173 | { 174 | "cell_type": "markdown", 175 | "id": "3412dd8d-958c-42da-bc26-0f021c832b7b", 176 | "metadata": { 177 | "id": "3d2edc14" 178 | }, 179 | "source": [ 180 | "We searched for `(organism_id:9606) AND (reviewed:true) AND (length:[80 TO 500])` on UniProt to get a list of reasonably-sized human proteins, then selected the format to TSV and the columns to `Accession`, `Sequence` and `Subcellular location [CC]`, since those contain the data we care about for this task." 181 | ] 182 | }, 183 | { 184 | "cell_type": "code", 185 | "execution_count": 4, 186 | "id": "0bae78eb-e690-4574-b110-16f4f6a8a2e3", 187 | "metadata": { 188 | "id": "dd03ef98" 189 | }, 190 | "outputs": [], 191 | "source": [ 192 | "uniprot_request = requests.get(query_url)" 193 | ] 194 | }, 195 | { 196 | "cell_type": "markdown", 197 | "id": "7494ca5e-f712-4b7b-9445-043942bc78a4", 198 | "metadata": { 199 | "id": "b7217b77" 200 | }, 201 | "source": [ 202 | "To get this data into Pandas, we use a `BytesIO` object, which Pandas will treat like a file. If you downloaded the data as a file you can skip this bit and just pass the filepath directly to `read_csv`." 203 | ] 204 | }, 205 | { 206 | "cell_type": "code", 207 | "execution_count": 5, 208 | "id": "6e2481a9-b84b-420b-8fab-aadddc5160ef", 209 | "metadata": { 210 | "colab": { 211 | "base_uri": "https://localhost:8080/", 212 | "height": 468 213 | }, 214 | "id": "f2c05017", 215 | "outputId": "9de817df-8a18-4ac3-b70b-452d8f6aa71a" 216 | }, 217 | "outputs": [ 218 | { 219 | "data": { 220 | "text/html": [ 221 | "
\n", 222 | "\n", 235 | "\n", 236 | " \n", 237 | " \n", 238 | " \n", 239 | " \n", 240 | " \n", 241 | " \n", 242 | " \n", 243 | " \n", 244 | " \n", 245 | " \n", 246 | " \n", 247 | " \n", 248 | " \n", 249 | " \n", 250 | " \n", 251 | " \n", 252 | " \n", 253 | " \n", 254 | " \n", 255 | " \n", 256 | " \n", 257 | " \n", 258 | " \n", 259 | " \n", 260 | " \n", 261 | " \n", 262 | " \n", 263 | " \n", 264 | " \n", 265 | " \n", 266 | " \n", 267 | " \n", 268 | " \n", 269 | " \n", 270 | " \n", 271 | " \n", 272 | " \n", 273 | " \n", 274 | " \n", 275 | " \n", 276 | "
EntrySequenceSubcellular location [CC]
0A0A0K2S4Q6MTQRAGAAMLPSALLLLCVPGCLTVSGPSTVMGAVGESLSVQCRYE...SUBCELLULAR LOCATION: [Isoform 1]: Membrane {E...
1A0AVI4MDSPEVTFTLAYLVFAVCFVFTPNEFHAAGLTVQNLLSGWLGSEDA...SUBCELLULAR LOCATION: Endoplasmic reticulum me...
2A0JLT2MENFTALFGAQADPPPPPTALGFGPGKPPPPPPPPAGGGPGTAPPP...SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
3A0M8Q6GQPKAAPSVTLFPPSSEELQANKATLVCLVSDFNPGAVTVAWKADG...SUBCELLULAR LOCATION: Secreted {ECO:0000303|Pu...
4A0PJY2MDSSCHNATTKMLATAPARGNMMSTSKPLAFSIERIMARTPEPKAL...SUBCELLULAR LOCATION: Nucleus {ECO:0000269|Pub...
\n", 277 | "
" 278 | ], 279 | "text/plain": [ 280 | " Entry Sequence \\\n", 281 | "0 A0A0K2S4Q6 MTQRAGAAMLPSALLLLCVPGCLTVSGPSTVMGAVGESLSVQCRYE... \n", 282 | "1 A0AVI4 MDSPEVTFTLAYLVFAVCFVFTPNEFHAAGLTVQNLLSGWLGSEDA... \n", 283 | "2 A0JLT2 MENFTALFGAQADPPPPPTALGFGPGKPPPPPPPPAGGGPGTAPPP... \n", 284 | "3 A0M8Q6 GQPKAAPSVTLFPPSSEELQANKATLVCLVSDFNPGAVTVAWKADG... \n", 285 | "4 A0PJY2 MDSSCHNATTKMLATAPARGNMMSTSKPLAFSIERIMARTPEPKAL... \n", 286 | "\n", 287 | " Subcellular location [CC] \n", 288 | "0 SUBCELLULAR LOCATION: [Isoform 1]: Membrane {E... \n", 289 | "1 SUBCELLULAR LOCATION: Endoplasmic reticulum me... \n", 290 | "2 SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. \n", 291 | "3 SUBCELLULAR LOCATION: Secreted {ECO:0000303|Pu... \n", 292 | "4 SUBCELLULAR LOCATION: Nucleus {ECO:0000269|Pub... " 293 | ] 294 | }, 295 | "execution_count": 5, 296 | "metadata": {}, 297 | "output_type": "execute_result" 298 | } 299 | ], 300 | "source": [ 301 | "from io import BytesIO\n", 302 | "import pandas as pd\n", 303 | "\n", 304 | "# read in content to dataframe\n", 305 | "bio = BytesIO(uniprot_request.content)\n", 306 | "df = pd.read_csv(bio, compression='gzip', sep='\\t')\n", 307 | "\n", 308 | "# check out first 5 rows of df\n", 309 | "df.head()" 310 | ] 311 | }, 312 | { 313 | "cell_type": "code", 314 | "execution_count": 6, 315 | "id": "ad5595c8-f8f1-42c3-aa53-cd332d7d38ac", 316 | "metadata": {}, 317 | "outputs": [ 318 | { 319 | "name": "stdout", 320 | "output_type": "stream", 321 | "text": [ 322 | "\n", 323 | "RangeIndex: 11980 entries, 0 to 11979\n", 324 | "Data columns (total 3 columns):\n", 325 | " # Column Non-Null Count Dtype \n", 326 | "--- ------ -------------- ----- \n", 327 | " 0 Entry 11980 non-null object\n", 328 | " 1 Sequence 11980 non-null object\n", 329 | " 2 Subcellular location [CC] 9840 non-null object\n", 330 | "dtypes: object(3)\n", 331 | "memory usage: 280.9+ KB\n" 332 | ] 333 | } 334 | ], 335 | "source": [ 336 | "# learn more about the df via .info() or .shape\n", 337 | "df.info()" 338 | ] 339 | }, 340 | { 341 | "cell_type": "markdown", 342 | "id": "650dc9bf-47d7-4faa-98eb-2a40da2e1938", 343 | "metadata": { 344 | "id": "0bcdf34b" 345 | }, 346 | "source": [ 347 | "Nice! Now we have some proteins and their subcellular locations. Let's start filtering this down. First, let's ditch the columns without subcellular location information." 348 | ] 349 | }, 350 | { 351 | "cell_type": "markdown", 352 | "id": "6badb1af-f4b8-46be-91cd-a75cb7a4c527", 353 | "metadata": {}, 354 | "source": [ 355 | "## Data Preparation" 356 | ] 357 | }, 358 | { 359 | "cell_type": "code", 360 | "execution_count": 7, 361 | "id": "a2291e81-9d2b-4411-8305-62a0a058ebfe", 362 | "metadata": { 363 | "id": "31d87663" 364 | }, 365 | "outputs": [], 366 | "source": [ 367 | "# Drop proteins with missing columns\n", 368 | "df = df.dropna() " 369 | ] 370 | }, 371 | { 372 | "cell_type": "code", 373 | "execution_count": 8, 374 | "id": "6d6f5b8b-455a-4c52-a47b-e3fc14467079", 375 | "metadata": {}, 376 | "outputs": [ 377 | { 378 | "name": "stdout", 379 | "output_type": "stream", 380 | "text": [ 381 | "\n", 382 | "Index: 9840 entries, 0 to 11969\n", 383 | "Data columns (total 3 columns):\n", 384 | " # Column Non-Null Count Dtype \n", 385 | "--- ------ -------------- ----- \n", 386 | " 0 Entry 9840 non-null object\n", 387 | " 1 Sequence 9840 non-null object\n", 388 | " 2 Subcellular location [CC] 9840 non-null object\n", 389 | "dtypes: object(3)\n", 390 | "memory usage: 307.5+ KB\n" 391 | ] 392 | } 393 | ], 394 | "source": [ 395 | "# check\n", 396 | "df.info()" 397 | ] 398 | }, 399 | { 400 | "cell_type": "markdown", 401 | "id": "311e56bd-dabc-4b2e-8f82-7a6da8538bed", 402 | "metadata": { 403 | "id": "10d1af5c" 404 | }, 405 | "source": [ 406 | "Now we'll make one dataframe of proteins that contain `cytosol` or `cytoplasm` in their subcellular localization column, and a second that mentions the `membrane` or `cell membrane`." 407 | ] 408 | }, 409 | { 410 | "cell_type": "code", 411 | "execution_count": 9, 412 | "id": "9f27cb39-8c94-4488-a446-7d0e9a031f23", 413 | "metadata": { 414 | "id": "c831bb16" 415 | }, 416 | "outputs": [], 417 | "source": [ 418 | "# first creating boolean series\n", 419 | "cytosolic = df['Subcellular location [CC]'].str.contains(\"Cytosol\") | df['Subcellular location [CC]'].str.contains(\"Cytoplasm\")\n", 420 | "membrane = df['Subcellular location [CC]'].str.contains(\"Membrane\") | df['Subcellular location [CC]'].str.contains(\"Cell membrane\")" 421 | ] 422 | }, 423 | { 424 | "cell_type": "markdown", 425 | "id": "36c3c8a5-a041-4566-994d-5601edfcc5c4", 426 | "metadata": {}, 427 | "source": [ 428 | "We ensure that there is no overlap between classes." 429 | ] 430 | }, 431 | { 432 | "cell_type": "code", 433 | "execution_count": 10, 434 | "id": "c3c7dec8-3f0e-4464-8997-184d9e580c90", 435 | "metadata": { 436 | "colab": { 437 | "base_uri": "https://localhost:8080/", 438 | "height": 424 439 | }, 440 | "id": "f41139a2", 441 | "outputId": "05884511-1ce7-435b-b5f5-16cf91ca973c" 442 | }, 443 | "outputs": [ 444 | { 445 | "data": { 446 | "text/html": [ 447 | "
\n", 448 | "\n", 461 | "\n", 462 | " \n", 463 | " \n", 464 | " \n", 465 | " \n", 466 | " \n", 467 | " \n", 468 | " \n", 469 | " \n", 470 | " \n", 471 | " \n", 472 | " \n", 473 | " \n", 474 | " \n", 475 | " \n", 476 | " \n", 477 | " \n", 478 | " \n", 479 | " \n", 480 | " \n", 481 | " \n", 482 | " \n", 483 | " \n", 484 | " \n", 485 | " \n", 486 | " \n", 487 | " \n", 488 | " \n", 489 | " \n", 490 | " \n", 491 | " \n", 492 | " \n", 493 | " \n", 494 | " \n", 495 | " \n", 496 | " \n", 497 | " \n", 498 | " \n", 499 | " \n", 500 | " \n", 501 | " \n", 502 | "
EntrySequenceSubcellular location [CC]
9A1E959MKIIILLGFLGATLSAPLIPQRLMSASNSNELLLNLNNGQLLPLQL...SUBCELLULAR LOCATION: Secreted {ECO:0000250|Un...
14A1XBS5MMRRTLENRNAQTKQLQTAVSNVEKHFGELCQIFAAYVRKTARLRD...SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|P...
18A2RU49MSSGNYQQSEALSKPTFSEEQASALVESVFGLKVSKVRPLPSYDDQ...SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
20A2RUH7MEAATAPEVAAGSKLKVKEASPADAEPPQASPGQGAGSPTPQLLPP...SUBCELLULAR LOCATION: Cytoplasm, myofibril, sa...
21A4D126MEAGPPGSARPAEPGPCLSGQRGADHTASASLQSVAGTEPGRHPQA...SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:...
\n", 503 | "
" 504 | ], 505 | "text/plain": [ 506 | " Entry Sequence \\\n", 507 | "9 A1E959 MKIIILLGFLGATLSAPLIPQRLMSASNSNELLLNLNNGQLLPLQL... \n", 508 | "14 A1XBS5 MMRRTLENRNAQTKQLQTAVSNVEKHFGELCQIFAAYVRKTARLRD... \n", 509 | "18 A2RU49 MSSGNYQQSEALSKPTFSEEQASALVESVFGLKVSKVRPLPSYDDQ... \n", 510 | "20 A2RUH7 MEAATAPEVAAGSKLKVKEASPADAEPPQASPGQGAGSPTPQLLPP... \n", 511 | "21 A4D126 MEAGPPGSARPAEPGPCLSGQRGADHTASASLQSVAGTEPGRHPQA... \n", 512 | "\n", 513 | " Subcellular location [CC] \n", 514 | "9 SUBCELLULAR LOCATION: Secreted {ECO:0000250|Un... \n", 515 | "14 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|P... \n", 516 | "18 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. \n", 517 | "20 SUBCELLULAR LOCATION: Cytoplasm, myofibril, sa... \n", 518 | "21 SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:... " 519 | ] 520 | }, 521 | "execution_count": 10, 522 | "metadata": {}, 523 | "output_type": "execute_result" 524 | } 525 | ], 526 | "source": [ 527 | "# use above booleans to filter df\n", 528 | "# NOTE: using .copy() when slicing/filtering an existing dataframe \n", 529 | "# prevents the triggering of 'SettingWithCopyWarning' \n", 530 | "cytosolic_df = df[cytosolic & ~membrane].copy()\n", 531 | "\n", 532 | "# check using .head() and/or .tail()\n", 533 | "cytosolic_df.head()" 534 | ] 535 | }, 536 | { 537 | "cell_type": "code", 538 | "execution_count": 11, 539 | "id": "97b8ade4-d39e-48a1-ad5a-7908faeb9331", 540 | "metadata": {}, 541 | "outputs": [ 542 | { 543 | "data": { 544 | "text/html": [ 545 | "
\n", 546 | "\n", 559 | "\n", 560 | " \n", 561 | " \n", 562 | " \n", 563 | " \n", 564 | " \n", 565 | " \n", 566 | " \n", 567 | " \n", 568 | " \n", 569 | " \n", 570 | " \n", 571 | " \n", 572 | " \n", 573 | " \n", 574 | " \n", 575 | " \n", 576 | " \n", 577 | " \n", 578 | " \n", 579 | " \n", 580 | " \n", 581 | " \n", 582 | " \n", 583 | " \n", 584 | " \n", 585 | " \n", 586 | " \n", 587 | " \n", 588 | " \n", 589 | " \n", 590 | " \n", 591 | " \n", 592 | " \n", 593 | " \n", 594 | " \n", 595 | " \n", 596 | " \n", 597 | " \n", 598 | " \n", 599 | " \n", 600 | "
EntrySequenceSubcellular location [CC]
11527Q8TDY3MFNPHALDSPAVIFDNGSGFCKAGLSGEFGPRHMVSSIVGHLKFQA...SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton ...
11540Q8WWF8MAGTARHDREMAIQAKKKLTTATDPIERLRLQCLARGSAGIKGLGR...SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
11665Q9NUJ7MGGQVSASNSFSRLHCRNANEDWMSALCPRLWDVPLHHLSIPGSHD...SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|P...
11667Q9NVM6MAVTKELLQMDLYALLGIEEKAADKEVKKAYRQKALSCHPDKNPDN...SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|U...
11675Q9P2W6MGRTWCGMWRRRRPGRRSAVPRWPHLSSQSGVEPPDRWTGTPGWPS...SUBCELLULAR LOCATION: Cytoplasm.
\n", 601 | "
" 602 | ], 603 | "text/plain": [ 604 | " Entry Sequence \\\n", 605 | "11527 Q8TDY3 MFNPHALDSPAVIFDNGSGFCKAGLSGEFGPRHMVSSIVGHLKFQA... \n", 606 | "11540 Q8WWF8 MAGTARHDREMAIQAKKKLTTATDPIERLRLQCLARGSAGIKGLGR... \n", 607 | "11665 Q9NUJ7 MGGQVSASNSFSRLHCRNANEDWMSALCPRLWDVPLHHLSIPGSHD... \n", 608 | "11667 Q9NVM6 MAVTKELLQMDLYALLGIEEKAADKEVKKAYRQKALSCHPDKNPDN... \n", 609 | "11675 Q9P2W6 MGRTWCGMWRRRRPGRRSAVPRWPHLSSQSGVEPPDRWTGTPGWPS... \n", 610 | "\n", 611 | " Subcellular location [CC] \n", 612 | "11527 SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton ... \n", 613 | "11540 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. \n", 614 | "11665 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|P... \n", 615 | "11667 SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|U... \n", 616 | "11675 SUBCELLULAR LOCATION: Cytoplasm. " 617 | ] 618 | }, 619 | "execution_count": 11, 620 | "metadata": {}, 621 | "output_type": "execute_result" 622 | } 623 | ], 624 | "source": [ 625 | "cytosolic_df.tail()" 626 | ] 627 | }, 628 | { 629 | "cell_type": "code", 630 | "execution_count": 12, 631 | "id": "ab5a996f-ca49-4f34-ac85-15b51ef09826", 632 | "metadata": { 633 | "colab": { 634 | "base_uri": "https://localhost:8080/", 635 | "height": 424 636 | }, 637 | "id": "be5c420e", 638 | "outputId": "2588389b-05e0-4707-8e93-9995880b2dee" 639 | }, 640 | "outputs": [ 641 | { 642 | "data": { 643 | "text/html": [ 644 | "
\n", 645 | "\n", 658 | "\n", 659 | " \n", 660 | " \n", 661 | " \n", 662 | " \n", 663 | " \n", 664 | " \n", 665 | " \n", 666 | " \n", 667 | " \n", 668 | " \n", 669 | " \n", 670 | " \n", 671 | " \n", 672 | " \n", 673 | " \n", 674 | " \n", 675 | " \n", 676 | " \n", 677 | " \n", 678 | " \n", 679 | " \n", 680 | " \n", 681 | " \n", 682 | " \n", 683 | " \n", 684 | " \n", 685 | " \n", 686 | " \n", 687 | " \n", 688 | " \n", 689 | " \n", 690 | " \n", 691 | " \n", 692 | " \n", 693 | " \n", 694 | " \n", 695 | " \n", 696 | " \n", 697 | " \n", 698 | " \n", 699 | "
EntrySequenceSubcellular location [CC]
0A0A0K2S4Q6MTQRAGAAMLPSALLLLCVPGCLTVSGPSTVMGAVGESLSVQCRYE...SUBCELLULAR LOCATION: [Isoform 1]: Membrane {E...
3A0M8Q6GQPKAAPSVTLFPPSSEELQANKATLVCLVSDFNPGAVTVAWKADG...SUBCELLULAR LOCATION: Secreted {ECO:0000303|Pu...
17A2RU14MAGTVLGVGAGVFILALLWVAVLLLCVLLSRASGAARFSVIFLFFG...SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ...
33A5X5Y0MEGSWFHRKRFSFYLLLGFLLQGRGVTFTINCSGFGQHGADPTALN...SUBCELLULAR LOCATION: Postsynaptic cell membra...
36A6ND01MACWWPLLLELWTVMPTWAGDELLNICMNAKHHKRVPSPEDKLYEE...SUBCELLULAR LOCATION: Cell membrane {ECO:00002...
\n", 700 | "
" 701 | ], 702 | "text/plain": [ 703 | " Entry Sequence \\\n", 704 | "0 A0A0K2S4Q6 MTQRAGAAMLPSALLLLCVPGCLTVSGPSTVMGAVGESLSVQCRYE... \n", 705 | "3 A0M8Q6 GQPKAAPSVTLFPPSSEELQANKATLVCLVSDFNPGAVTVAWKADG... \n", 706 | "17 A2RU14 MAGTVLGVGAGVFILALLWVAVLLLCVLLSRASGAARFSVIFLFFG... \n", 707 | "33 A5X5Y0 MEGSWFHRKRFSFYLLLGFLLQGRGVTFTINCSGFGQHGADPTALN... \n", 708 | "36 A6ND01 MACWWPLLLELWTVMPTWAGDELLNICMNAKHHKRVPSPEDKLYEE... \n", 709 | "\n", 710 | " Subcellular location [CC] \n", 711 | "0 SUBCELLULAR LOCATION: [Isoform 1]: Membrane {E... \n", 712 | "3 SUBCELLULAR LOCATION: Secreted {ECO:0000303|Pu... \n", 713 | "17 SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ... \n", 714 | "33 SUBCELLULAR LOCATION: Postsynaptic cell membra... \n", 715 | "36 SUBCELLULAR LOCATION: Cell membrane {ECO:00002... " 716 | ] 717 | }, 718 | "execution_count": 12, 719 | "metadata": {}, 720 | "output_type": "execute_result" 721 | } 722 | ], 723 | "source": [ 724 | "# use boolean series to filter df\n", 725 | "membrane_df = df[membrane & ~cytosolic].copy()\n", 726 | "\n", 727 | "# check\n", 728 | "membrane_df.head()" 729 | ] 730 | }, 731 | { 732 | "cell_type": "code", 733 | "execution_count": 13, 734 | "id": "7a0596b8-6655-4000-a8f6-555b961b84ab", 735 | "metadata": {}, 736 | "outputs": [ 737 | { 738 | "data": { 739 | "text/html": [ 740 | "
\n", 741 | "\n", 754 | "\n", 755 | " \n", 756 | " \n", 757 | " \n", 758 | " \n", 759 | " \n", 760 | " \n", 761 | " \n", 762 | " \n", 763 | " \n", 764 | " \n", 765 | " \n", 766 | " \n", 767 | " \n", 768 | " \n", 769 | " \n", 770 | " \n", 771 | " \n", 772 | " \n", 773 | " \n", 774 | " \n", 775 | " \n", 776 | " \n", 777 | " \n", 778 | " \n", 779 | " \n", 780 | " \n", 781 | " \n", 782 | " \n", 783 | " \n", 784 | " \n", 785 | " \n", 786 | " \n", 787 | " \n", 788 | " \n", 789 | " \n", 790 | " \n", 791 | " \n", 792 | " \n", 793 | " \n", 794 | " \n", 795 | "
EntrySequenceSubcellular location [CC]
11896Q86UQ5MQSDIYHPGHSFPSWVLCWVHSCGHEGHLRETAEIRKTHQNGDLQI...SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ...
11920Q8N8V8MLLKVRRASLKPPATPHQGAFRAGNVIGQLIYLLTWSLFTAWLRPP...SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ...
11959Q96N68MQGQGALKESHIHLPTEQPEASLVLQGQLAESSALGPKGALRPQAQ...SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ...
11966Q9H0A3MMNNTDFLMLNNPWNKLCLVSMDFCFPLDFVSNLFWIFASKFIIVT...SUBCELLULAR LOCATION: Membrane {ECO:0000255}; ...
11969Q9H354MNKHNLRLVQLASELILIEIIPKLFLSQVTTISHIKREKIPPNHRK...SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ...
\n", 796 | "
" 797 | ], 798 | "text/plain": [ 799 | " Entry Sequence \\\n", 800 | "11896 Q86UQ5 MQSDIYHPGHSFPSWVLCWVHSCGHEGHLRETAEIRKTHQNGDLQI... \n", 801 | "11920 Q8N8V8 MLLKVRRASLKPPATPHQGAFRAGNVIGQLIYLLTWSLFTAWLRPP... \n", 802 | "11959 Q96N68 MQGQGALKESHIHLPTEQPEASLVLQGQLAESSALGPKGALRPQAQ... \n", 803 | "11966 Q9H0A3 MMNNTDFLMLNNPWNKLCLVSMDFCFPLDFVSNLFWIFASKFIIVT... \n", 804 | "11969 Q9H354 MNKHNLRLVQLASELILIEIIPKLFLSQVTTISHIKREKIPPNHRK... \n", 805 | "\n", 806 | " Subcellular location [CC] \n", 807 | "11896 SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ... \n", 808 | "11920 SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ... \n", 809 | "11959 SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ... \n", 810 | "11966 SUBCELLULAR LOCATION: Membrane {ECO:0000255}; ... \n", 811 | "11969 SUBCELLULAR LOCATION: Membrane {ECO:0000305}; ... " 812 | ] 813 | }, 814 | "execution_count": 13, 815 | "metadata": {}, 816 | "output_type": "execute_result" 817 | } 818 | ], 819 | "source": [ 820 | "membrane_df.tail()" 821 | ] 822 | }, 823 | { 824 | "cell_type": "markdown", 825 | "id": "9798179a-96ac-42d3-959e-79cd9564a63c", 826 | "metadata": { 827 | "id": "77e8cea6" 828 | }, 829 | "source": [ 830 | "Now, let's add labels. We use `0` as the label for cytosolic proteins and `1` as the label for membrane proteins." 831 | ] 832 | }, 833 | { 834 | "cell_type": "code", 835 | "execution_count": 14, 836 | "id": "4ff5bbdb-6f11-4d9e-995a-2019f1338b73", 837 | "metadata": {}, 838 | "outputs": [], 839 | "source": [ 840 | "# adding label columns\n", 841 | "cytosolic_df['label'] = 0\n", 842 | "membrane_df['label'] = 1" 843 | ] 844 | }, 845 | { 846 | "cell_type": "markdown", 847 | "id": "e430cec6-fb0c-45db-8854-52e9d37014a2", 848 | "metadata": { 849 | "id": "5a4bbda2" 850 | }, 851 | "source": [ 852 | "Now we will combine the 2 groups to form our initial dataset. Don't worry - the proteins will get shuffled when splitting the data!" 853 | ] 854 | }, 855 | { 856 | "cell_type": "code", 857 | "execution_count": 15, 858 | "id": "a589d77f-7c63-4b5c-b584-8a4ca8f3d4cb", 859 | "metadata": {}, 860 | "outputs": [ 861 | { 862 | "name": "stdout", 863 | "output_type": "stream", 864 | "text": [ 865 | "\n", 866 | "Index: 5170 entries, 9 to 11969\n", 867 | "Data columns (total 2 columns):\n", 868 | " # Column Non-Null Count Dtype \n", 869 | "--- ------ -------------- ----- \n", 870 | " 0 Sequence 5170 non-null object\n", 871 | " 1 label 5170 non-null int64 \n", 872 | "dtypes: int64(1), object(1)\n", 873 | "memory usage: 121.2+ KB\n" 874 | ] 875 | } 876 | ], 877 | "source": [ 878 | "# combining dataframes and only keeping 'Sequence' and 'label' columns\n", 879 | "df_sequences = pd.concat([cytosolic_df, membrane_df])[['Sequence', 'label']]\n", 880 | "\n", 881 | "# check\n", 882 | "df_sequences.info()" 883 | ] 884 | }, 885 | { 886 | "cell_type": "code", 887 | "execution_count": 16, 888 | "id": "2edbec8f-e266-4a47-92b5-5679eba48aa8", 889 | "metadata": {}, 890 | "outputs": [ 891 | { 892 | "data": { 893 | "text/plain": [ 894 | "label\n", 895 | "0 0.509284\n", 896 | "1 0.490716\n", 897 | "Name: proportion, dtype: float64" 898 | ] 899 | }, 900 | "execution_count": 16, 901 | "metadata": {}, 902 | "output_type": "execute_result" 903 | } 904 | ], 905 | "source": [ 906 | "# check class distribution\n", 907 | "df_sequences['label'].value_counts(normalize=True)" 908 | ] 909 | }, 910 | { 911 | "cell_type": "markdown", 912 | "id": "79fdd50c-9531-4baa-a9a5-5e8e66521fc0", 913 | "metadata": {}, 914 | "source": [ 915 | "We can also see that we will be working with a dataset with a balanced number of observations per class. " 916 | ] 917 | }, 918 | { 919 | "cell_type": "markdown", 920 | "id": "46d6f5a5-416b-4e74-8f11-ff574ceaf9b6", 921 | "metadata": { 922 | "id": "e0aac39c" 923 | }, 924 | "source": [ 925 | "### Splitting the data" 926 | ] 927 | }, 928 | { 929 | "cell_type": "markdown", 930 | "id": "c2c00e81-f9b2-44af-b798-9b9029c0a5fc", 931 | "metadata": { 932 | "id": "a9099e7c" 933 | }, 934 | "source": [ 935 | "We need to split the data into train and test sets. We can use sklearn's function for that:" 936 | ] 937 | }, 938 | { 939 | "cell_type": "code", 940 | "execution_count": 17, 941 | "id": "99b8a8bb-658c-42ad-a6b4-03cea93e6b13", 942 | "metadata": { 943 | "id": "366147ad" 944 | }, 945 | "outputs": [], 946 | "source": [ 947 | "from sklearn.model_selection import train_test_split\n", 948 | "\n", 949 | "train_sequences, test_sequences, train_labels, test_labels = train_test_split(\n", 950 | " df_sequences['Sequence'], \n", 951 | " df_sequences['label'],\n", 952 | " test_size=0.2,\n", 953 | " shuffle=True, #default\n", 954 | " stratify=df_sequences['label']\n", 955 | ")" 956 | ] 957 | }, 958 | { 959 | "cell_type": "markdown", 960 | "id": "f0fcd94a-31be-4771-9a94-15de903183c2", 961 | "metadata": {}, 962 | "source": [ 963 | "### Quick EDA of the datasets" 964 | ] 965 | }, 966 | { 967 | "cell_type": "code", 968 | "execution_count": 18, 969 | "id": "14faf07e-a4ef-4a24-a31e-2e532afad27f", 970 | "metadata": {}, 971 | "outputs": [], 972 | "source": [ 973 | "from Bio.SeqUtils.ProtParam import ProteinAnalysis\n", 974 | "\n", 975 | "# recall this function from seq_analysis.ipynb\n", 976 | "# calculates mean amino acid composition for a set of sequences\n", 977 | "def calculate_mean_AA_composition(sequences):\n", 978 | " stats = []\n", 979 | " for sequence in sequences:\n", 980 | " protein_sequence = ProteinAnalysis(sequence)\n", 981 | " st = {k:v/len(sequence) for k,v in protein_sequence.count_amino_acids().items()}\n", 982 | " stats.append(st)\n", 983 | " df = pd.DataFrame.from_dict(stats).transpose()\n", 984 | " df = df.T.mean().reset_index()\n", 985 | " df.columns = ['amino acid', 'mean']\n", 986 | "\n", 987 | " return df" 988 | ] 989 | }, 990 | { 991 | "cell_type": "code", 992 | "execution_count": 19, 993 | "id": "f71e6845-85b1-490b-b1fd-420097446346", 994 | "metadata": {}, 995 | "outputs": [], 996 | "source": [ 997 | "train_df = calculate_mean_AA_composition(train_sequences)\n", 998 | "test_df = calculate_mean_AA_composition(test_sequences)" 999 | ] 1000 | }, 1001 | { 1002 | "cell_type": "code", 1003 | "execution_count": 20, 1004 | "id": "8516588d-974d-4974-a142-b55b78cf6e19", 1005 | "metadata": {}, 1006 | "outputs": [ 1007 | { 1008 | "data": { 1009 | "application/vnd.plotly.v1+json": { 1010 | "config": { 1011 | "plotlyServerURL": "https://plot.ly" 1012 | }, 1013 | "data": [ 1014 | { 1015 | "alignmentgroup": "True", 1016 | "hovertemplate": "amino acid=%{x}
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"gridcolor": "white", 1952 | "linecolor": "white", 1953 | "ticks": "", 1954 | "title": { 1955 | "standoff": 15 1956 | }, 1957 | "zerolinecolor": "white", 1958 | "zerolinewidth": 2 1959 | }, 1960 | "yaxis": { 1961 | "automargin": true, 1962 | "gridcolor": "white", 1963 | "linecolor": "white", 1964 | "ticks": "", 1965 | "title": { 1966 | "standoff": 15 1967 | }, 1968 | "zerolinecolor": "white", 1969 | "zerolinewidth": 2 1970 | } 1971 | } 1972 | }, 1973 | "xaxis": { 1974 | "anchor": "y", 1975 | "domain": [ 1976 | 0, 1977 | 1 1978 | ], 1979 | "title": { 1980 | "text": "amino acid" 1981 | } 1982 | }, 1983 | "yaxis": { 1984 | "anchor": "x", 1985 | "domain": [ 1986 | 0, 1987 | 1 1988 | ], 1989 | "title": { 1990 | "text": "mean" 1991 | } 1992 | } 1993 | } 1994 | } 1995 | }, 1996 | "metadata": {}, 1997 | "output_type": "display_data" 1998 | } 1999 | ], 2000 | "source": [ 2001 | "import plotly.express as px\n", 2002 | "import plotly.io as pio\n", 2003 | "#pio.renderers.default = 'colab'\n", 2004 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"gridcolor": "white", 2960 | "linecolor": "white", 2961 | "ticks": "", 2962 | "title": { 2963 | "standoff": 15 2964 | }, 2965 | "zerolinecolor": "white", 2966 | "zerolinewidth": 2 2967 | }, 2968 | "yaxis": { 2969 | "automargin": true, 2970 | "gridcolor": "white", 2971 | "linecolor": "white", 2972 | "ticks": "", 2973 | "title": { 2974 | "standoff": 15 2975 | }, 2976 | "zerolinecolor": "white", 2977 | "zerolinewidth": 2 2978 | } 2979 | } 2980 | }, 2981 | "xaxis": { 2982 | "anchor": "y", 2983 | "domain": [ 2984 | 0, 2985 | 1 2986 | ], 2987 | "title": { 2988 | "text": "amino acid" 2989 | } 2990 | }, 2991 | "yaxis": { 2992 | "anchor": "x", 2993 | "domain": [ 2994 | 0, 2995 | 1 2996 | ], 2997 | "title": { 2998 | "text": "mean" 2999 | } 3000 | } 3001 | } 3002 | } 3003 | }, 3004 | "metadata": {}, 3005 | "output_type": "display_data" 3006 | } 3007 | ], 3008 | "source": [ 3009 | "fig = px.bar(test_df.sort_values('mean'), x='amino acid', y='mean', color='mean')\n", 3010 | "fig.show()" 3011 | ] 3012 | }, 3013 | { 3014 | "cell_type": "markdown", 3015 | "id": "504bc7e9-d8a2-4edf-83a0-58b94c0eddda", 3016 | "metadata": { 3017 | "id": "7d29b4ed" 3018 | }, 3019 | "source": [ 3020 | "## Tokenisation" 3021 | ] 3022 | }, 3023 | { 3024 | "cell_type": "markdown", 3025 | "id": "ad4ea3fe-1a7d-41f6-b214-4ef3a3c1fea5", 3026 | "metadata": { 3027 | "id": "c02baaf7" 3028 | }, 3029 | "source": [ 3030 | "All inputs to neural nets must be numerical. The process of converting strings into numerical indices suitable for a neural net is called **tokenization**. For natural language this can be quite complex, as usually the network's vocabulary will not contain every possible word, which means the tokenizer must handle splitting rarer words into pieces, as well as all the complexities of capitalization and unicode characters and so on.\n", 3031 | "\n", 3032 | "With proteins, however, things are very easy. In protein language models, each amino acid is converted to a single token. Every model on `transformers` comes with an associated `tokenizer` that handles tokenization for it, and protein language models are no different. Let's get our tokenizer!" 3033 | ] 3034 | }, 3035 | { 3036 | "cell_type": "code", 3037 | "execution_count": 22, 3038 | "id": "245c56d6-f03b-4306-80f5-0678b051a822", 3039 | "metadata": { 3040 | "colab": { 3041 | "base_uri": "https://localhost:8080/", 3042 | "height": 113, 3043 | "referenced_widgets": [ 3044 | "48ea66931f1e4eec9c02d44766897106", 3045 | "799fbc24f6d745a89716caaf7e2db87a", 3046 | "62f8ae11792145bea1b1d7afd1497415", 3047 | "e151623066004c969cb6258f70adcde9", 3048 | "994d3df7154e403fb1e29185bb73d714", 3049 | "b6cf9d5576c14031a9fc901bf1c83284", 3050 | "0d4c7cec0152401e9faa3145bef7cbb0", 3051 | "69d9d37fdee24c7cacac2c4a88df0273", 3052 | "8ecac32695454023a98d889893340a4d", 3053 | "008851fc6aec47e6b9294343f281d4ef", 3054 | "881d61da2cc64f0aba9cd11d99d18044", 3055 | "f6e1a4cbf15249628dae2f4c2a51f8cf", 3056 | "d74c66158e8343988e937573a5254c4c", 3057 | "db52d20520bf44798ce76323e4324b80", 3058 | "ef065a30ea9246dfb9b7e4ac96b58ca9", 3059 | "591e3f5003b2422e8aa55ab750226195", 3060 | "7b51332c344a4d73a13327d0448f499f", 3061 | "ef8c06dbfc70495d9d38ffbbf83aeb8d", 3062 | "df6b40fa9fb84c788b860bd3a8ec814e", 3063 | "ea16a9e174e74dcb98b9a5b5229725b5", 3064 | "4a15581db7dd4f8cbf1bd92493ff9587", 3065 | "6e5a3b7598cb466fb327ff99f8c2331c", 3066 | "1769f6420fb845c9935c0cecc4f14189", 3067 | "04b87e010c234a518bf102462b65c758", 3068 | "6d486f76da1e422e83943af3143bc567", 3069 | "fc4e48d289104bfea7348a3e8f74bf13", 3070 | "c41e121a002b4235b6f9dc35ea0bd5f0", 3071 | "64e999c2e40041f7beb5baf4c3a8fefb", 3072 | "5f5a22e1a2c043bf9cb02816628c1f49", 3073 | "3aa54d54e9da433c91b35983e50795ab", 3074 | "635d2a69bb9648e68fc161d2927da091", 3075 | "ddbb89e848a343f29b28d38ea7aa0e39", 3076 | "68fd265ae06542299ea9a1ec664537b5" 3077 | ] 3078 | }, 3079 | "id": "ddbe2b2d", 3080 | "outputId": "41950c4a-22fc-4018-838c-fbbcbc421482" 3081 | }, 3082 | "outputs": [], 3083 | "source": [ 3084 | "from transformers import AutoTokenizer\n", 3085 | "tokenizer = AutoTokenizer.from_pretrained(model_checkpoint)" 3086 | ] 3087 | }, 3088 | { 3089 | "cell_type": "markdown", 3090 | "id": "776e3399-4c54-48c7-ad0e-71ee5fb57e9c", 3091 | "metadata": { 3092 | "id": "9d16be37" 3093 | }, 3094 | "source": [ 3095 | "Let's try a single sequence to see what the outputs from our tokenizer look like:" 3096 | ] 3097 | }, 3098 | { 3099 | "cell_type": "code", 3100 | "execution_count": 23, 3101 | "id": "dc349a74-8b06-40a5-9889-65b144ef763d", 3102 | "metadata": { 3103 | "colab": { 3104 | "base_uri": "https://localhost:8080/" 3105 | }, 3106 | "id": "687386af", 3107 | "outputId": "a55bc023-b94b-4ef3-fb34-cac712bdf9cf" 3108 | }, 3109 | "outputs": [ 3110 | { 3111 | "data": { 3112 | "text/plain": [ 3113 | "{'input_ids': [0, 20, 11, 16, 10, 5, 6, 5, 5, 20, 4, 14, 8, 5, 4, 4, 4, 4, 23, 7, 14, 6, 23, 4, 11, 7, 8, 6, 14, 8, 11, 7, 20, 6, 5, 7, 6, 9, 8, 4, 8, 7, 16, 23, 10, 19, 9, 9, 15, 19, 15, 11, 18, 17, 15, 19, 22, 23, 10, 16, 14, 23, 4, 14, 12, 22, 21, 9, 20, 7, 9, 11, 6, 6, 8, 9, 6, 7, 7, 10, 8, 13, 16, 7, 12, 12, 11, 13, 21, 14, 6, 13, 4, 11, 18, 11, 7, 11, 4, 9, 17, 4, 11, 5, 13, 13, 5, 6, 15, 19, 10, 23, 6, 12, 5, 11, 12, 4, 16, 9, 13, 6, 4, 8, 6, 18, 4, 14, 13, 14, 18, 18, 16, 7, 16, 7, 4, 7, 8, 8, 5, 8, 8, 11, 9, 17, 8, 7, 15, 11, 14, 5, 8, 14, 11, 10, 14, 8, 16, 23, 16, 6, 8, 4, 14, 8, 8, 11, 23, 18, 4, 4, 4, 14, 4, 4, 15, 7, 14, 4, 4, 4, 8, 12, 4, 6, 5, 12, 4, 22, 7, 17, 10, 14, 22, 10, 11, 14, 22, 11, 9, 8, 2], 'attention_mask': [1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1]}" 3114 | ] 3115 | }, 3116 | "execution_count": 23, 3117 | "metadata": {}, 3118 | "output_type": "execute_result" 3119 | } 3120 | ], 3121 | "source": [ 3122 | "tokenizer(train_sequences.to_list()[0])" 3123 | ] 3124 | }, 3125 | { 3126 | "cell_type": "markdown", 3127 | "id": "00830f7d-ddc6-4fcb-a7b9-d4193c3d2f6d", 3128 | "metadata": { 3129 | "id": "9a719808" 3130 | }, 3131 | "source": [ 3132 | "This looks good! We can see that our sequence has been converted into `input_ids`, which is the tokenized sequence, and an `attention_mask`. The attention mask handles the case when we have sequences of variable length - in those cases, the shorter sequences are padded with blank \"padding\" tokens, and the attention mask is padded with 0s to indicate that those tokens should be ignored by the model.\n", 3133 | "\n", 3134 | "So now, let's tokenize our whole dataset. Note that we don't need to do anything with the labels, as they're already in the format we need." 3135 | ] 3136 | }, 3137 | { 3138 | "cell_type": "code", 3139 | "execution_count": 24, 3140 | "id": "3781e8d3-8f07-469e-a651-147a02f1cba8", 3141 | "metadata": { 3142 | "id": "56e26ddf" 3143 | }, 3144 | "outputs": [], 3145 | "source": [ 3146 | "# tokenize train and test sequences, which need to be list of str\n", 3147 | "train_tokenized = tokenizer(train_sequences.tolist())\n", 3148 | "test_tokenized = tokenizer(test_sequences.tolist())" 3149 | ] 3150 | }, 3151 | { 3152 | "cell_type": "markdown", 3153 | "id": "d8646c13-b638-4b49-928c-23a1caa4e5a1", 3154 | "metadata": { 3155 | "id": "df3681d1" 3156 | }, 3157 | "source": [ 3158 | "## Training Dataset creation" 3159 | ] 3160 | }, 3161 | { 3162 | "cell_type": "markdown", 3163 | "id": "2ec84852-18b3-43db-a953-397997cf7d7b", 3164 | "metadata": { 3165 | "id": "85089e49" 3166 | }, 3167 | "source": [ 3168 | "Now we want to turn this data into a dataset that PyTorch can load samples from. We can use the HuggingFace `Dataset` class for this, although if you prefer you can also use `torch.utils.data.Dataset`, at the cost of some more boilerplate code ([Datasets](https://pytorch.org/tutorials/beginner/basics/data_tutorial.html))." 3169 | ] 3170 | }, 3171 | { 3172 | "cell_type": "code", 3173 | "execution_count": 25, 3174 | "id": "c6b1fde6-00c6-4930-b2d4-2b21038dc725", 3175 | "metadata": { 3176 | "colab": { 3177 | "base_uri": "https://localhost:8080/" 3178 | }, 3179 | "id": "fb79ba6c", 3180 | "outputId": "5c355205-9071-4994-bd63-af320efc97bb" 3181 | }, 3182 | "outputs": [ 3183 | { 3184 | "data": { 3185 | "text/plain": [ 3186 | "Dataset({\n", 3187 | " features: ['input_ids', 'attention_mask'],\n", 3188 | " num_rows: 4136\n", 3189 | "})" 3190 | ] 3191 | }, 3192 | "execution_count": 25, 3193 | "metadata": {}, 3194 | "output_type": "execute_result" 3195 | } 3196 | ], 3197 | "source": [ 3198 | "from datasets import Dataset\n", 3199 | "\n", 3200 | "train_dataset = Dataset.from_dict(train_tokenized)\n", 3201 | "test_dataset = Dataset.from_dict(test_tokenized)\n", 3202 | "\n", 3203 | "# check\n", 3204 | "train_dataset" 3205 | ] 3206 | }, 3207 | { 3208 | "cell_type": "markdown", 3209 | "id": "b8e2a6c0-efbf-4b9f-ac11-2bafc6777ff5", 3210 | "metadata": { 3211 | "id": "9e809e47" 3212 | }, 3213 | "source": [ 3214 | "This looks good, but we're missing our labels! Let's add those on as an extra column to the datasets." 3215 | ] 3216 | }, 3217 | { 3218 | "cell_type": "code", 3219 | "execution_count": 26, 3220 | "id": "3697fdbb-e43b-4d48-b481-4e3e90ee97f4", 3221 | "metadata": { 3222 | "colab": { 3223 | "base_uri": "https://localhost:8080/" 3224 | }, 3225 | "id": "090acc0d", 3226 | "outputId": "a14a5583-d946-47f1-d0a6-b31514d7325e" 3227 | }, 3228 | "outputs": [ 3229 | { 3230 | "data": { 3231 | "text/plain": [ 3232 | "Dataset({\n", 3233 | " features: ['input_ids', 'attention_mask', 'labels'],\n", 3234 | " num_rows: 4136\n", 3235 | "})" 3236 | ] 3237 | }, 3238 | "execution_count": 26, 3239 | "metadata": {}, 3240 | "output_type": "execute_result" 3241 | } 3242 | ], 3243 | "source": [ 3244 | "train_dataset = train_dataset.add_column(\"labels\", train_labels)\n", 3245 | "test_dataset = test_dataset.add_column(\"labels\", test_labels)\n", 3246 | "\n", 3247 | "# check\n", 3248 | "train_dataset" 3249 | ] 3250 | }, 3251 | { 3252 | "cell_type": "markdown", 3253 | "id": "e6d38664-d28d-4e70-97c7-e055fe4ed90f", 3254 | "metadata": {}, 3255 | "source": [ 3256 | "We will split the training set further to use a subset of the data to evaluate the model during fine-tuning (i.e., validation dataset)." 3257 | ] 3258 | }, 3259 | { 3260 | "cell_type": "code", 3261 | "execution_count": 27, 3262 | "id": "841ffd19-2bef-436e-8b26-f5a75ff6ec36", 3263 | "metadata": {}, 3264 | "outputs": [ 3265 | { 3266 | "data": { 3267 | "text/plain": [ 3268 | "DatasetDict({\n", 3269 | " train: Dataset({\n", 3270 | " features: ['input_ids', 'attention_mask', 'labels'],\n", 3271 | " num_rows: 3308\n", 3272 | " })\n", 3273 | " test: Dataset({\n", 3274 | " features: ['input_ids', 'attention_mask', 'labels'],\n", 3275 | " num_rows: 828\n", 3276 | " })\n", 3277 | "})" 3278 | ] 3279 | }, 3280 | "execution_count": 27, 3281 | "metadata": {}, 3282 | "output_type": "execute_result" 3283 | } 3284 | ], 3285 | "source": [ 3286 | "train_val_dataset = train_dataset.train_test_split(test_size=0.2)\n", 3287 | "\n", 3288 | "# check\n", 3289 | "train_val_dataset" 3290 | ] 3291 | }, 3292 | { 3293 | "cell_type": "markdown", 3294 | "id": "815741ed-b125-4661-825f-6f126272fdde", 3295 | "metadata": { 3296 | "id": "ced9aaa8" 3297 | }, 3298 | "source": [ 3299 | "Looks good! We're ready for training." 3300 | ] 3301 | }, 3302 | { 3303 | "cell_type": "markdown", 3304 | "id": "dda2901c-0d02-473e-baa6-d3bdcaa9dd42", 3305 | "metadata": { 3306 | "id": "af074a5c" 3307 | }, 3308 | "source": [ 3309 | "## Model loading" 3310 | ] 3311 | }, 3312 | { 3313 | "cell_type": "markdown", 3314 | "id": "e2bd5289-8d5a-4977-b49e-d8deeb072795", 3315 | "metadata": { 3316 | "id": "ccab5d70" 3317 | }, 3318 | "source": [ 3319 | "Next, we want to load our model. Make sure to use exactly the same model as you used when loading the tokenizer, or your model might not understand the tokenization scheme you're using!" 3320 | ] 3321 | }, 3322 | { 3323 | "cell_type": "code", 3324 | "execution_count": 28, 3325 | "id": "8cf7b3c8-a150-4552-8e2e-8913563ad214", 3326 | "metadata": { 3327 | "colab": { 3328 | "base_uri": "https://localhost:8080/", 3329 | "height": 570, 3330 | "referenced_widgets": [ 3331 | "cd93caa975e74791aba3ede7889c058c", 3332 | "8f7654f0423b48668a983802e6a6aa44", 3333 | "8b9f0a93dcfa4ce08f831355bc82c861", 3334 | "4385c61c3462447c9f6d5a53298fb237", 3335 | "55213ae044de4d9582bcae84c8da9ef6", 3336 | "7908d984799d4d65a398c03346e26729", 3337 | "03618d81301b47ba83336698ffa9c2b7", 3338 | "b003ddf9b40946d690681825979f8205", 3339 | "56e04648858b4965ad94e32c3b26a2f6", 3340 | "cae4138fb556439a994edefcce4e6bd3", 3341 | "e0a77469998a47bd9f39a28403c5ec6c", 3342 | "901a5c1ebca34d899b203035d23c0f46", 3343 | "ce7b83f8fa9649d7b11cce43001198bb", 3344 | "8ede690fe0874410b347a48c276915e7", 3345 | "91c00e196504498a9e5c2d4391b4c0f7", 3346 | "f177f5bd5dfa4765b6eb6bd8ae091348", 3347 | "ec71fad4a3cd4815aff289e25ef70de2", 3348 | "9949f236e90b45c2ba921ce479e54920", 3349 | "b0d02c8c223346b5bf9ab6c7569b9eff", 3350 | "20764cdac47445c09985f2204024d7f6", 3351 | "71f7ff0a7df84d0898dbf14ac3808165", 3352 | "406d2f83ccad49ec9cb114f78d8514a9", 3353 | "8a5fbf0a1e6042f3b1d3900a1d854c2a", 3354 | "8e94130dc4a64b56a156d1bff4c90131", 3355 | "e6c6841a50474f7daef5b1ec9a0f1b79", 3356 | "37329fa50e0a4f3fbb2f863fc9150a40", 3357 | "039c8434f6564960a846b49998e6dc98", 3358 | "8697aee2b4fe469eb8b2acf4c93934cc", 3359 | "ecdf7a23e3be42b1a98d6206221a005d", 3360 | "641ba6628d1c43138343987f6a102a7c", 3361 | "8e3718c5e1e846bca36cacc19f481d7b", 3362 | "30fedea993de40e5962816ded086afa7", 3363 | "a2b96cc7bf62480f8c08e49a79c54e91", 3364 | "d906e65029ec46cca5d4c8736c790535", 3365 | "6360234a90c44caa8d9bbf7b6833fc9f", 3366 | "57893132e5be4b2baca0db3dadd46999", 3367 | "eafbb78481fb41f8a9792eb5e8a00043", 3368 | "fd88fadcbd9e449f9ba6938013d58f7c", 3369 | "290af5dfc2b3470b94e07a96d982c6b1", 3370 | "0384b6458894415a95142dd26902e47f", 3371 | "4434eef7462e44b8a77ebfa30b15de19", 3372 | "262dfa94f2404e3caf3c3bb81215eedf", 3373 | "9a5a74ef3a294b2cbaeb3a2968bffef9", 3374 | "c0b5bfdf1f6247dfb4e967c750fdd16d", 3375 | "ee83891aacff4186a2e5b1c015d5aa48", 3376 | "b9da13013ccb471fb46066fd37216ec1", 3377 | "cb854268a04c4857b8f641575150257a", 3378 | "f066f129604e47bb975acd5f2fb380f9", 3379 | "46a7dc72b34c4a80b4df01d7e2130412", 3380 | "0b3b862d04c14d61af5b08ad2c00895b", 3381 | "affc17d525b245a9a7df95f3ed5ecce5", 3382 | "16f52a411b3c4f10b986d85de862e34b", 3383 | "3f8103fe9c5e49449c0e39f4f1603f02", 3384 | "fb46882705784e1fb516ce156fa8f86e", 3385 | "0c0c429e800041bfa1530080d7b26400", 3386 | "f8bf3aebff25499fae5de8d82704fb6f", 3387 | "9ea7802e962e4647acf36aa0a42a86d2", 3388 | "28b1f101ef3749819f86b69349ce6c24", 3389 | "dcf594b86fce4062b0e624e6b7d996aa", 3390 | "7cb1942781ba4a6e9619d2cfca17dd5b", 3391 | "d6ba55fbcc20433a84a79478acd4f1ff", 3392 | "2d4f570d845540f8bbcce3a40d0026a7", 3393 | "ef7cbb1b37f84c208897c447ed6612da", 3394 | "559694d417154050b2712a6441e56f7d", 3395 | "758e1a01f3bd4c79a6833560c22e03f9", 3396 | "dfe14fbaae0e484f9bec2dd4bcb414ca", 3397 | "e4ca5fcd11964869901ed46cdfb4479a", 3398 | "82583bb78f6c446a9b374db27a1c262e", 3399 | "79c8f3195f0f4e3fb07c045cef8504de", 3400 | "7890cb3c089148bf9f63d9d45fc7b41f", 3401 | "95e819c3b93d443595704b14a6aceebc", 3402 | "7d2248b1c05644db9cc3b44e31a46cc1", 3403 | "73d0ece7c54d4e339d2d5bac0855aa58", 3404 | "89a06e969be9432d9294f9c7ff9b8675", 3405 | "6efb8d2b82c54e828de047e2c2b29efd", 3406 | "44b959e9df0b438799d99d57f6e313a6", 3407 | "4c6a54049338417e811f39d9ea54b33f" 3408 | ] 3409 | }, 3410 | "id": "fc164b49", 3411 | "outputId": "032629cb-2e91-478d-fd25-c6a179b3f26b" 3412 | }, 3413 | "outputs": [ 3414 | { 3415 | "data": { 3416 | "application/vnd.jupyter.widget-view+json": { 3417 | "model_id": "db65f495f247487f87b1bd5c147d6073", 3418 | "version_major": 2, 3419 | "version_minor": 0 3420 | }, 3421 | "text/plain": [ 3422 | "config.json: 0%| | 0.00/778 [00:00"] 6 | readme = "README.md" 7 | 8 | [tool.poetry.dependencies] 9 | python = "^3.11" 10 | transformers = {extras = ["torch"], version = "^4.47.1"} 11 | datasets = "^3.2.0" 12 | evaluate = "^0.4.3" 13 | biopython = "^1.84" 14 | py3dmol = "^2.4.2" 15 | pymsaviz = "^0.5.0" 16 | ipykernel = "^6.29.5" 17 | plotly = "^5.24.1" 18 | nbformat = "^5.10.4" 19 | jupyter = "^1.1.1" 20 | ipywidgets = "^8.1.5" 21 | pandas = "^2.2.3" 22 | scikit-learn = "^1.6.0" 23 | sentencepiece = "^0.2.0" 24 | h5py = "^3.12.1" 25 | 26 | 27 | [build-system] 28 | requires = ["poetry-core"] 29 | build-backend = "poetry.core.masonry.api" 30 | -------------------------------------------------------------------------------- /requirements.txt: -------------------------------------------------------------------------------- 1 | accelerate==1.2.1 ; python_version >= "3.11" and python_version < "4.0" 2 | aiohappyeyeballs==2.4.4 ; python_version >= "3.11" and python_version < "4.0" 3 | aiohttp==3.11.11 ; python_version >= "3.11" and python_version < "4.0" 4 | aiosignal==1.3.2 ; python_version >= "3.11" and python_version < "4.0" 5 | anyio==4.8.0 ; python_version >= "3.11" and python_version < "4.0" 6 | appnope==0.1.4 ; python_version >= "3.11" and python_version < "4.0" and platform_system == "Darwin" 7 | argon2-cffi-bindings==21.2.0 ; python_version >= "3.11" and python_version < "4.0" 8 | argon2-cffi==23.1.0 ; python_version >= "3.11" and python_version < "4.0" 9 | arrow==1.3.0 ; python_version >= "3.11" and python_version < "4.0" 10 | asttokens==3.0.0 ; python_version >= "3.11" and python_version < "4.0" 11 | async-lru==2.0.4 ; python_version >= "3.11" and python_version < "4.0" 12 | attrs==24.3.0 ; python_version >= "3.11" and python_version < "4.0" 13 | babel==2.16.0 ; python_version >= "3.11" and python_version < "4.0" 14 | beautifulsoup4==4.12.3 ; python_version >= "3.11" and python_version < "4.0" 15 | biopython==1.84 ; python_version >= "3.11" and python_version < "4.0" 16 | bleach[css]==6.2.0 ; python_version >= "3.11" and python_version < "4.0" 17 | certifi==2024.12.14 ; python_version >= "3.11" and python_version < "4.0" 18 | cffi==1.17.1 ; python_version >= "3.11" and python_version < "4.0" 19 | charset-normalizer==3.4.1 ; python_version >= "3.11" and python_version < "4.0" 20 | colorama==0.4.6 ; python_version >= "3.11" and python_version < "4.0" and (platform_system == "Windows" or sys_platform == "win32") 21 | comm==0.2.2 ; python_version >= "3.11" and python_version < "4.0" 22 | contourpy==1.3.1 ; python_version >= "3.11" and python_version < "4.0" 23 | cycler==0.12.1 ; python_version >= "3.11" and python_version < "4.0" 24 | datasets==3.2.0 ; python_version >= "3.11" and python_version < "4.0" 25 | debugpy==1.8.11 ; python_version >= "3.11" and python_version < "4.0" 26 | decorator==5.1.1 ; python_version >= "3.11" and python_version < "4.0" 27 | defusedxml==0.7.1 ; python_version >= "3.11" and python_version < "4.0" 28 | dill==0.3.8 ; python_version >= "3.11" and python_version < "4.0" 29 | evaluate==0.4.3 ; python_version >= "3.11" and python_version < "4.0" 30 | executing==2.1.0 ; python_version >= "3.11" and python_version < "4.0" 31 | fastjsonschema==2.21.1 ; python_version >= "3.11" and python_version < "4.0" 32 | filelock==3.16.1 ; python_version >= "3.11" and python_version < "4.0" 33 | fonttools==4.55.3 ; python_version >= "3.11" and python_version < "4.0" 34 | fqdn==1.5.1 ; python_version >= "3.11" and python_version < "4" 35 | frozenlist==1.5.0 ; python_version >= "3.11" and python_version < "4.0" 36 | fsspec==2024.9.0 ; python_version >= "3.11" and python_version < "4.0" 37 | fsspec[http]==2024.9.0 ; python_version >= "3.11" and python_version < "4.0" 38 | h11==0.14.0 ; python_version >= "3.11" and python_version < "4.0" 39 | h5py==3.12.1 ; python_version >= "3.11" and python_version < "4.0" 40 | httpcore==1.0.7 ; python_version >= "3.11" and python_version < "4.0" 41 | httpx==0.28.1 ; python_version >= "3.11" and python_version < "4.0" 42 | huggingface-hub==0.27.1 ; python_version >= "3.11" and python_version < "4.0" 43 | idna==3.10 ; python_version >= "3.11" and python_version < "4.0" 44 | ipykernel==6.29.5 ; python_version >= "3.11" and python_version < "4.0" 45 | ipython==8.31.0 ; python_version >= "3.11" and python_version < "4.0" 46 | ipywidgets==8.1.5 ; python_version >= "3.11" and python_version < "4.0" 47 | isoduration==20.11.0 ; python_version >= "3.11" and python_version < "4.0" 48 | jedi==0.19.2 ; python_version >= "3.11" and python_version < "4.0" 49 | jinja2==3.1.5 ; python_version >= "3.11" and python_version < "4.0" 50 | joblib==1.4.2 ; python_version >= "3.11" and python_version < "4.0" 51 | json5==0.10.0 ; python_version >= "3.11" and python_version < "4.0" 52 | jsonpointer==3.0.0 ; python_version >= "3.11" and python_version < "4.0" 53 | jsonschema-specifications==2024.10.1 ; python_version >= "3.11" and python_version < "4.0" 54 | jsonschema==4.23.0 ; python_version >= "3.11" and python_version < "4.0" 55 | jsonschema[format-nongpl]==4.23.0 ; python_version >= "3.11" and python_version < "4.0" 56 | jupyter-client==8.6.3 ; python_version >= "3.11" and python_version < "4.0" 57 | jupyter-console==6.6.3 ; python_version >= "3.11" and python_version < "4.0" 58 | jupyter-core==5.7.2 ; python_version >= "3.11" and python_version < "4.0" 59 | jupyter-events==0.11.0 ; python_version >= "3.11" and python_version < "4.0" 60 | jupyter-lsp==2.2.5 ; python_version >= "3.11" and python_version < "4.0" 61 | jupyter-server-terminals==0.5.3 ; python_version >= "3.11" and python_version < "4.0" 62 | jupyter-server==2.15.0 ; python_version >= "3.11" and python_version < "4.0" 63 | jupyter==1.1.1 ; python_version >= "3.11" and python_version < "4.0" 64 | jupyterlab-pygments==0.3.0 ; python_version >= "3.11" and python_version < "4.0" 65 | jupyterlab-server==2.27.3 ; python_version >= "3.11" and python_version < "4.0" 66 | jupyterlab-widgets==3.0.13 ; python_version >= "3.11" and python_version < "4.0" 67 | jupyterlab==4.3.4 ; python_version >= "3.11" and python_version < "4.0" 68 | kiwisolver==1.4.8 ; python_version >= "3.11" and python_version < "4.0" 69 | markupsafe==3.0.2 ; python_version >= "3.11" and python_version < "4.0" 70 | matplotlib-inline==0.1.7 ; python_version >= "3.11" and python_version < "4.0" 71 | matplotlib==3.10.0 ; python_version >= "3.11" and python_version < "4.0" 72 | mistune==3.1.0 ; python_version >= "3.11" and python_version < "4.0" 73 | mpmath==1.3.0 ; python_version >= "3.11" and python_version < "4.0" 74 | multidict==6.1.0 ; python_version >= "3.11" and python_version < "4.0" 75 | multiprocess==0.70.16 ; python_version >= "3.11" and python_version < "4.0" 76 | nbclient==0.10.2 ; python_version >= "3.11" and python_version < "4.0" 77 | nbconvert==7.16.5 ; python_version >= "3.11" and python_version < "4.0" 78 | nbformat==5.10.4 ; python_version >= "3.11" and python_version < "4.0" 79 | nest-asyncio==1.6.0 ; python_version >= "3.11" and python_version < "4.0" 80 | networkx==3.4.2 ; python_version >= "3.11" and python_version < "4.0" 81 | notebook-shim==0.2.4 ; python_version >= "3.11" and python_version < "4.0" 82 | notebook==7.3.2 ; python_version >= "3.11" and python_version < "4.0" 83 | numpy==2.2.1 ; python_version >= "3.11" and python_version < "4.0" 84 | nvidia-cublas-cu12==12.4.5.8 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 85 | nvidia-cuda-cupti-cu12==12.4.127 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 86 | nvidia-cuda-nvrtc-cu12==12.4.127 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 87 | nvidia-cuda-runtime-cu12==12.4.127 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 88 | nvidia-cudnn-cu12==9.1.0.70 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 89 | nvidia-cufft-cu12==11.2.1.3 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 90 | nvidia-curand-cu12==10.3.5.147 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 91 | nvidia-cusolver-cu12==11.6.1.9 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 92 | nvidia-cusparse-cu12==12.3.1.170 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 93 | nvidia-nccl-cu12==2.21.5 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 94 | nvidia-nvjitlink-cu12==12.4.127 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 95 | nvidia-nvtx-cu12==12.4.127 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version >= "3.11" and python_version < "4.0" 96 | overrides==7.7.0 ; python_version >= "3.11" and python_version < "4.0" 97 | packaging==24.2 ; python_version >= "3.11" and python_version < "4.0" 98 | pandas==2.2.3 ; python_version >= "3.11" and python_version < "4.0" 99 | pandocfilters==1.5.1 ; python_version >= "3.11" and python_version < "4.0" 100 | parso==0.8.4 ; python_version >= "3.11" and python_version < "4.0" 101 | pexpect==4.9.0 ; python_version >= "3.11" and python_version < "4.0" and (sys_platform != "win32" and sys_platform != "emscripten") 102 | pillow==11.1.0 ; python_version >= "3.11" and python_version < "4.0" 103 | platformdirs==4.3.6 ; python_version >= "3.11" and python_version < "4.0" 104 | plotly==5.24.1 ; python_version >= "3.11" and python_version < "4.0" 105 | prometheus-client==0.21.1 ; python_version >= "3.11" and python_version < "4.0" 106 | prompt-toolkit==3.0.48 ; python_version >= "3.11" and python_version < "4.0" 107 | propcache==0.2.1 ; python_version >= "3.11" and python_version < "4.0" 108 | psutil==6.1.1 ; python_version >= "3.11" and python_version < "4.0" 109 | ptyprocess==0.7.0 ; python_version >= "3.11" and python_version < "4.0" and (sys_platform != "win32" and sys_platform != "emscripten" or os_name != "nt") 110 | pure-eval==0.2.3 ; python_version >= "3.11" and python_version < "4.0" 111 | py3dmol==2.4.2 ; python_version >= "3.11" and python_version < "4.0" 112 | pyarrow==18.1.0 ; python_version >= "3.11" and python_version < "4.0" 113 | pycparser==2.22 ; python_version >= "3.11" and python_version < "4.0" 114 | pygments==2.19.1 ; python_version >= "3.11" and python_version < "4.0" 115 | pymsaviz==0.5.0 ; python_version >= "3.11" and python_version < "4.0" 116 | pyparsing==3.2.1 ; python_version >= "3.11" and python_version < "4.0" 117 | python-dateutil==2.9.0.post0 ; python_version >= "3.11" and python_version < "4.0" 118 | python-json-logger==3.2.1 ; python_version >= "3.11" and python_version < "4.0" 119 | pytz==2024.2 ; python_version >= "3.11" and python_version < "4.0" 120 | pywin32==308 ; sys_platform == "win32" and platform_python_implementation != "PyPy" and python_version >= "3.11" and python_version < "4.0" 121 | pywinpty==2.0.14 ; python_version >= "3.11" and python_version < "4.0" and os_name == "nt" 122 | pyyaml==6.0.2 ; python_version >= "3.11" and python_version < "4.0" 123 | pyzmq==26.2.0 ; python_version >= "3.11" and python_version < "4.0" 124 | referencing==0.35.1 ; python_version >= "3.11" and python_version < "4.0" 125 | regex==2024.11.6 ; python_version >= "3.11" and python_version < "4.0" 126 | requests==2.32.3 ; python_version >= "3.11" and python_version < "4.0" 127 | rfc3339-validator==0.1.4 ; python_version >= "3.11" and python_version < "4.0" 128 | rfc3986-validator==0.1.1 ; python_version >= "3.11" and python_version < "4.0" 129 | rpds-py==0.22.3 ; python_version >= "3.11" and python_version < "4.0" 130 | safetensors==0.5.1 ; python_version >= "3.11" and python_version < "4.0" 131 | scikit-learn==1.6.0 ; python_version >= "3.11" and python_version < "4.0" 132 | scipy==1.15.0 ; python_version >= "3.11" and python_version < "4.0" 133 | send2trash==1.8.3 ; python_version >= "3.11" and python_version < "4.0" 134 | sentencepiece==0.2.0 ; python_version >= "3.11" and python_version < "4.0" 135 | setuptools==75.7.0 ; python_version >= "3.11" and python_version < "4.0" 136 | six==1.17.0 ; python_version >= "3.11" and python_version < "4.0" 137 | sniffio==1.3.1 ; python_version >= "3.11" and python_version < "4.0" 138 | soupsieve==2.6 ; python_version >= "3.11" and python_version < "4.0" 139 | stack-data==0.6.3 ; python_version >= "3.11" and python_version < "4.0" 140 | sympy==1.13.1 ; python_version >= "3.11" and python_version < "4.0" 141 | tenacity==9.0.0 ; python_version >= "3.11" and python_version < "4.0" 142 | terminado==0.18.1 ; python_version >= "3.11" and python_version < "4.0" 143 | threadpoolctl==3.5.0 ; python_version >= "3.11" and python_version < "4.0" 144 | tinycss2==1.4.0 ; python_version >= "3.11" and python_version < "4.0" 145 | tokenizers==0.21.0 ; python_version >= "3.11" and python_version < "4.0" 146 | torch==2.5.1 ; python_version >= "3.11" and python_version < "4.0" 147 | tornado==6.4.2 ; python_version >= "3.11" and python_version < "4.0" 148 | tqdm==4.67.1 ; python_version >= "3.11" and python_version < "4.0" 149 | traitlets==5.14.3 ; python_version >= "3.11" and python_version < "4.0" 150 | transformers[torch]==4.47.1 ; python_version >= "3.11" and python_version < "4.0" 151 | triton==3.1.0 ; platform_system == "Linux" and platform_machine == "x86_64" and python_version < "3.13" and python_version >= "3.11" 152 | types-python-dateutil==2.9.0.20241206 ; python_version >= "3.11" and python_version < "4.0" 153 | typing-extensions==4.12.2 ; python_version >= "3.11" and python_version < "4.0" 154 | tzdata==2024.2 ; python_version >= "3.11" and python_version < "4.0" 155 | uri-template==1.3.0 ; python_version >= "3.11" and python_version < "4.0" 156 | urllib3==2.3.0 ; python_version >= "3.11" and python_version < "4.0" 157 | wcwidth==0.2.13 ; python_version >= "3.11" and python_version < "4.0" 158 | webcolors==24.11.1 ; python_version >= "3.11" and python_version < "4.0" 159 | webencodings==0.5.1 ; python_version >= "3.11" and python_version < "4.0" 160 | websocket-client==1.8.0 ; python_version >= "3.11" and python_version < "4.0" 161 | widgetsnbextension==4.0.13 ; python_version >= "3.11" and python_version < "4.0" 162 | xxhash==3.5.0 ; python_version >= "3.11" and python_version < "4.0" 163 | yarl==1.18.3 ; python_version >= "3.11" and python_version < "4.0" 164 | -------------------------------------------------------------------------------- /slides/intro_pLM.key: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/slides/intro_pLM.key -------------------------------------------------------------------------------- /slides/intro_pLM.pdf: -------------------------------------------------------------------------------- https://raw.githubusercontent.com/Multiomics-Analytics-Group/course_protein_language_modeling/37c74ceb67f32c138a7a7e6a6cc2c6baccffcfef/slides/intro_pLM.pdf -------------------------------------------------------------------------------- /topics.md: -------------------------------------------------------------------------------- 1 | # Protein Language Modeling Course 2 | 3 | 4 | ## Topics 5 | ---- 6 | **1. Proteins** 7 | 8 | What are they and why are they important. 9 | 10 | **2. The Language of Proteins: Sequences** 11 | 12 | Analyzing the amino acid sequence of a protein, including aligning sequences, identifying patterns, and utilizing databases and resources to gain insights into protein function and evolution. 13 | 14 | **3. Protein Structure** 15 | 16 | Predicting the three-dimensional structure of a protein using computational methods, including homology modeling, comparative modeling, and de novo structure prediction. 17 | 18 | **4. Protein-Protein Interactions** 19 | 20 | Exploring how proteins interact with each other, including computational techniques for predicting and analyzing protein-protein interactions, as well as docking algorithms for simulating their binding. 21 | 22 | **5. Protein Engineering and Design** 23 | 24 | Modifying proteins to enhance their properties or design new ones, using methods like directed evolution and rational design, often guided by computational modeling and simulation. 25 | 26 | **6. Protein Function Prediction and Annotation** 27 | 28 | Inferring the function of a protein based on its sequence or structure, utilizing computational methods to predict and annotate protein functions, including predicting protein-protein interactions. 29 | 30 | **7. Data Resources** 31 | 32 | A description of resources that contain relevant protein data that can be used in ML models. 33 | 34 | **8. Machine Learning and Deep Learning for Protein Language Modeling** 35 | 36 | Leveraging machine learning and deep learning algorithms to model and analyze protein sequences and structures, enabling tasks such as sequence generation, structure prediction, and function annotation. 37 | 38 | **9. Applications of Protein Language Models** 39 | 40 | Exploring real-world applications of protein language modeling, including refining and improving protein structures, predicting protein-protein interactions, facilitating drug discovery, and aiding protein engineering and design. 41 | 42 | **10. Limitations** 43 | 44 | Addressing the limitations associated with protein language modeling, potential biases or shortcomings of computational methods. 45 | --------------------------------------------------------------------------------