Bidirectional Learning for Offline Model-based Biological Sequence Design

Can Chen, Yingxue Zhang, Xue Liu, Mark Coates
Proceedings of the 40th International Conference on Machine Learning, PMLR 202:5351-5366, 2023.

Abstract

Offline model-based optimization aims to maximize a black-box objective function with a static dataset of designs and their scores. In this paper, we focus on biological sequence design to maximize some sequence score. A recent approach employs bidirectional learning, combining a forward mapping for exploitation and a backward mapping for constraint, and it relies on the neural tangent kernel (NTK) of an infinitely wide network to build a proxy model. Though effective, the NTK cannot learn features because of its parametrization, and its use prevents the incorporation of powerful pre-trained Language Models (LMs) that can capture the rich biophysical information in millions of biological sequences. We adopt an alternative proxy model, adding a linear head to a pre-trained LM, and propose a linearization scheme. This yields a closed-form loss and also takes into account the biophysical information in the pre-trained LM. In addition, the forward mapping and the backward mapping play different roles and thus deserve different weights during sequence optimization. To achieve this, we train an auxiliary model and leverage its weak supervision signal via a bi-level optimization framework to effectively learn how to balance the two mappings. Further, by extending the framework, we develop the first learning rate adaptation module Adaptive-$\eta$, which is compatible with all gradient-based algorithms for offline model-based optimization. Experimental results on DNA/protein sequence design tasks verify the effectiveness of our algorithm. Our code is available at https://github.com/GGchen1997/BIB-ICML2023-Submission.

Cite this Paper

BibTeX
@InProceedings{pmlr-v202-chen23ao, title = {Bidirectional Learning for Offline Model-based Biological Sequence Design}, author = {Chen, Can and Zhang, Yingxue and Liu, Xue and Coates, Mark}, booktitle = {Proceedings of the 40th International Conference on Machine Learning}, pages = {5351--5366}, year = {2023}, editor = {Krause, Andreas and Brunskill, Emma and Cho, Kyunghyun and Engelhardt, Barbara and Sabato, Sivan and Scarlett, Jonathan}, volume = {202}, series = {Proceedings of Machine Learning Research}, month = {23--29 Jul}, publisher = {PMLR}, pdf = {https://proceedings.mlr.press/v202/chen23ao/chen23ao.pdf}, url = {https://proceedings.mlr.press/v202/chen23ao.html}, abstract = {Offline model-based optimization aims to maximize a black-box objective function with a static dataset of designs and their scores. In this paper, we focus on biological sequence design to maximize some sequence score. A recent approach employs bidirectional learning, combining a forward mapping for exploitation and a backward mapping for constraint, and it relies on the neural tangent kernel (NTK) of an infinitely wide network to build a proxy model. Though effective, the NTK cannot learn features because of its parametrization, and its use prevents the incorporation of powerful pre-trained Language Models (LMs) that can capture the rich biophysical information in millions of biological sequences. We adopt an alternative proxy model, adding a linear head to a pre-trained LM, and propose a linearization scheme. This yields a closed-form loss and also takes into account the biophysical information in the pre-trained LM. In addition, the forward mapping and the backward mapping play different roles and thus deserve different weights during sequence optimization. To achieve this, we train an auxiliary model and leverage its weak supervision signal via a bi-level optimization framework to effectively learn how to balance the two mappings. Further, by extending the framework, we develop the first learning rate adaptation module Adaptive-$\eta$, which is compatible with all gradient-based algorithms for offline model-based optimization. Experimental results on DNA/protein sequence design tasks verify the effectiveness of our algorithm. Our code is available at https://github.com/GGchen1997/BIB-ICML2023-Submission.} }
Endnote
%0 Conference Paper %T Bidirectional Learning for Offline Model-based Biological Sequence Design %A Can Chen %A Yingxue Zhang %A Xue Liu %A Mark Coates %B Proceedings of the 40th International Conference on Machine Learning %C Proceedings of Machine Learning Research %D 2023 %E Andreas Krause %E Emma Brunskill %E Kyunghyun Cho %E Barbara Engelhardt %E Sivan Sabato %E Jonathan Scarlett %F pmlr-v202-chen23ao %I PMLR %P 5351--5366 %U https://proceedings.mlr.press/v202/chen23ao.html %V 202 %X Offline model-based optimization aims to maximize a black-box objective function with a static dataset of designs and their scores. In this paper, we focus on biological sequence design to maximize some sequence score. A recent approach employs bidirectional learning, combining a forward mapping for exploitation and a backward mapping for constraint, and it relies on the neural tangent kernel (NTK) of an infinitely wide network to build a proxy model. Though effective, the NTK cannot learn features because of its parametrization, and its use prevents the incorporation of powerful pre-trained Language Models (LMs) that can capture the rich biophysical information in millions of biological sequences. We adopt an alternative proxy model, adding a linear head to a pre-trained LM, and propose a linearization scheme. This yields a closed-form loss and also takes into account the biophysical information in the pre-trained LM. In addition, the forward mapping and the backward mapping play different roles and thus deserve different weights during sequence optimization. To achieve this, we train an auxiliary model and leverage its weak supervision signal via a bi-level optimization framework to effectively learn how to balance the two mappings. Further, by extending the framework, we develop the first learning rate adaptation module Adaptive-$\eta$, which is compatible with all gradient-based algorithms for offline model-based optimization. Experimental results on DNA/protein sequence design tasks verify the effectiveness of our algorithm. Our code is available at https://github.com/GGchen1997/BIB-ICML2023-Submission.
APA
Chen, C., Zhang, Y., Liu, X. & Coates, M.. (2023). Bidirectional Learning for Offline Model-based Biological Sequence Design. Proceedings of the 40th International Conference on Machine Learning, in Proceedings of Machine Learning Research 202:5351-5366 Available from https://proceedings.mlr.press/v202/chen23ao.html.

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