Chuang Zhou, Zhu Wang, Shengyuan Chen, Jiahe Du, Qiyuan Zheng, Zhaozhuo Xu, Xiao Huang. Proceedings of the 63rd Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2025.

Modeling text-attributed graphs is a well-known problem due to the difficulty of capturing both the text attribute and the graph structure effectively. Existing models often focus on either the text attribute or the graph structure, potentially neglecting the other aspect. This is primarily because both text learning and graph learning models require significant computational resources, making it impractical to directly connect these models in a series. However, there are situations where text-learning models correctly classify text-attributed nodes, while graph-learning models may classify them incorrectly, and vice versa. To fully leverage the potential of text-attributed graphs, we propose a Coupled Text-attributed Graph Learning (CTGL) framework that combines the strengths of both text-learning and graph-learning models in parallel and avoids the computational cost of serially connecting the two aspect models. Specifically, CTGL introduces coupled text-graph augmentation to enable coupled contrastive learning and facilitate the exchange of valuable information between text learning and graph learning. Experimental results on diverse datasets demonstrate the superior performance of our model compared to state-of-the-art text-learning and graph-learning baselines.

Generating novel enzymes for target molecules in zero-shot scenarios is a fundamental challenge in biomaterial synthesis and chemical production. Without known enzymes for a target molecule, training generative models becomes difficult due to the lack of direct supervision. To address this, we propose a retrieval-augmented generation method that uses existing enzyme-substrate data to guide enzyme design. Our method retrieves enzymes with substrates that share structural similarities with the target molecule, leveraging functional similarities in catalytic activity. Since none of the retrieved enzymes directly catalyze the target molecule, we use a conditioned discrete diffusion model to generate new enzymes based on the retrieved examples. An enzyme-substrate relationship classifier guides the generation process to ensure optimal protein sequence distributions. We evaluate our model on enzyme design tasks with diverse real-world substrates and show that it outperforms existing protein generation methods in catalytic capability, foldability, and docking accuracy. Additionally, we define the zero-shot substrate-specified enzyme generation task and introduce a dataset with evaluation benchmarks.