Concept Bottleneck Language Models For Protein Design
Aya Abdelsalam Ismail, Tuomas P. Oikarinen, Amy Wang, Julius Adebayo, Samuel Don Stanton, Héctor Corrada Bravo, Kyunghyun Cho, Nathan C. Frey
Abstract
We introduce Concept Bottleneck Protein Language Models (CB-pLM) 1 , a generative masked language model with a layer where each neuron corresponds to an interpretable concept. Our architecture offers three key benefits: i) Control: We can intervene on concept values to precisely control the properties of generated proteins, achieving a 3× larger change in desired concept values compared to baselines. ii) Interpretability: A linear mapping between concept values and predicted tokens allows transparent analysis of the model's decision-making process. iii) Debugging: This transparency facilitates easy debugging of trained models. Our models achieve pre-training perplexity and downstream task performance comparable to traditional masked protein language models, demonstrating that interpretability does not compromise performance. While adaptable to any language model, we focus on masked protein language models due to their importance in drug discovery and the ability to validate our model's capabilities through realworld experiments and expert knowledge. We scale our CB-pLM from 24 million to 3 billion parameters, making them the largest Concept Bottleneck Models trained and the first capable of generative language modeling.
Ask about this paper
Your agent reads all of it.
Lune indexed this paper to the last equation, along with the top-tier papers that cite it. Ask a question and the answer quotes them.
Your agent calls
Luneget_paper_fulltext
Free to start. No credit card required.
Terminal
Install the CLIlune papers fulltext 61aec55a-5d1d-4ded-a69f-4d914a17043eCited by top-tier papers8
- Object-Centric Concept-BottlenecksDavid Steinmann, Wolfgang Stammer, Antonia Wüst, Kristian KerstingNeurIPS 2025 · 12 citations
- Controlling Repetition in Protein Language ModelsJiahao Zhang, Zeqing Zhang, Di Wang, Lijie HuICLR 2026 · 5 citations
- From Black-box to Causal-box: Towards Building More Interpretable ModelsInwoo Hwang, Yushu Pan, Elias BareinboimNeurIPS 2025 · 3 citations
- Mixture of Concept Bottleneck ExpertsFrancesco De Santis, Gabriele Ciravegna, Giovanni De Felice, Arianna Casanova et al.ICML 2026 · 2 citations
- ProtSAE: Disentangling and Interpreting Protein Language Models via Semantically-Guided Sparse AutoencodersXiangyu Liu, Haodi Lei, Yi Liu, Yang Liu et al.AAAI 2026 · 2 citations
Builds on16
- Language Models are Few-Shot LearnersTom B. Brown, Benjamin Mann, Nick Ryder, Melanie Subbiah et al.NeurIPS 2020 · 64,255 citations
- Concept Bottleneck ModelsPang Wei Koh, Thao Nguyen, Yew Siang Tang, Stephen Mussmann et al.ICML 2020 · 1,233 citations
- Sparse Autoencoders Find Highly Interpretable Features in Language ModelsRobert Huben, Hoagy Cunningham, Logan Riggs Smith, Aidan Ewart et al.ICLR 2024 · 1,072 citations
- Protein Design with Guided Discrete DiffusionNate Gruver, Samuel Stanton, Nathan C. Frey, Tim G. J. Rudner et al.NeurIPS 2023 · 246 citations
- Addressing Leakage in Concept Bottleneck ModelsMarton Havasi, Sonali Parbhoo, Finale Doshi-VelezNeurIPS 2022 · 163 citations
Related papers
- Concept Bottleneck Large Language ModelsChung-En Sun, Tuomas P. Oikarinen, Berk Ustun, Tsui-Wei WengICLR 2025
- VLG-CBM: Training Concept Bottleneck Models with Vision-Language GuidanceDivyansh Srivastava, Ge Yan, Lily WengNeurIPS 2024 · 87 citations
- Bayesian Concept Bottleneck Models with LLM PriorsJean Feng, Avni Kothari, Lucas Zier, Chandan Singh et al.NeurIPS 2025 · 23 citations
- Concept Bottleneck Generative ModelsAya Abdelsalam Ismail, Julius Adebayo, Héctor Corrada Bravo, Stephen Ra et al.ICLR 2024 · 43 citations
- Explanation Bottleneck ModelsShin'ya Yamaguchi, Kosuke NishidaAAAI 2025 · 4 citations
