Jianyu Shi

Guoxing Yang, Jianyu Shi, Zan Wang et al.

Pre-training and fine-tuning have emerged as a promising paradigm across various natural language processing (NLP) tasks. The effectiveness of pretrained large language models (LLM) has witnessed further enhancement, holding potential for applications in the field of medicine, particularly in the context of Traditional Chinese Medicine (TCM). However, the application of these general models to specific domains often yields suboptimal results, primarily due to challenges like lack of domain knowledge, unique objectives, and computational efficiency. Furthermore, their effectiveness in specialized domains, such as Traditional Chinese Medicine, requires comprehensive evaluation. To address the above issues, we propose a novel domain specific TCMDA (TCM Domain Adaptation) approach, efficient pre-training with domain-specific corpus. Specifically, we first construct a large TCM-specific corpus, TCM-Corpus-1B, by identifying domain keywords and retreving from general corpus. Then, our TCMDA leverages the LoRA which freezes the pretrained model's weights and uses rank decomposition matrices to efficiently train specific dense layers for pre-training and fine-tuning, efficiently aligning the model with TCM-related tasks, namely TCM-GPT-7B. We further conducted extensive experiments on two TCM tasks, including TCM examination and TCM diagnosis. TCM-GPT-7B archived the best performance across both datasets, outperforming other models by relative increments of 17% and 12% in accuracy, respectively. To the best of our knowledge, our study represents the pioneering validation of domain adaptation of a large language model with 7 billion parameters in TCM domain. We will release both TCMCorpus-1B and TCM-GPT-7B model once accepted to facilitate interdisciplinary development in TCM and NLP, serving as the foundation for further study.

Chao Song, Zhiyuan Liu, Han Huang et al.

Designing enzyme backbones with substrate-specific functionality is a critical challenge in computational protein engineering. Current generative models excel in protein design but face limitations in binding data, substrate-specific control, and flexibility for de novo enzyme backbone generation. To address this, we introduce EnzyBind, a dataset with 11,100 experimentally validated enzyme-substrate pairs specifically curated from PDBbind. Building on this, we propose EnzyControl, a method that enables functional and substrate-specific control in enzyme backbone generation. Our approach generates enzyme backbones conditioned on MSA-annotated catalytic sites and their corresponding substrates, which are automatically extracted from curated enzyme-substrate data. At the core of EnzyControl is EnzyAdapter, a lightweight, modular component integrated into a pretrained motif-scaffolding model, allowing it to become substrate-aware. A two-stage training paradigm further refines the model's ability to generate accurate and functional enzyme structures. Experiments show that our EnzyControl achieves the best performance across structural and functional metrics on EnzyBind and EnzyBench benchmarks, with particularly notable improvements of 13\% in designability and 13\% in catalytic efficiency compared to the baseline models. The code is released at https://github.com/Vecteur-libre/EnzyControl.

Hui Yu, ShiYu Zhao, JianYu Shi

Motivation: Computational prediction of multiple-type drug-drug interaction (DDI) helps reduce unexpected side effects in poly-drug treatments. Although existing computational approaches achieve inspiring results, they ignore that the action of a drug is mainly caused by its chemical substructures. In addition, their interpretability is still weak. Results: In this paper, by supposing that the interactions between two given drugs are caused by their local chemical structures (sub-structures) and their DDI types are determined by the linkages between different substructure sets, we design a novel Substructure-ware Tensor Neural Network model for DDI prediction (STNN-DDI). The proposed model learns a 3-D tensor of (substructure, in-teraction type, substructure) triplets, which characterizes a substructure-substructure interaction (SSI) space. According to a list of predefined substructures with specific chemical meanings, the mapping of drugs into this SSI space enables STNN-DDI to perform the multiple-type DDI prediction in both transductive and inductive scenarios in a unified form with an explicable manner. The compar-ison with deep learning-based state-of-the-art baselines demonstrates the superiority of STNN-DDI with the significant improvement of AUC, AUPR, Accuracy, and Precision. More importantly, case studies illustrate its interpretability by both revealing a crucial sub-structure pair across drugs regarding a DDI type of interest and uncovering interaction type-specific substructure pairs in a given DDI. In summary, STNN-DDI provides an effective approach to predicting DDIs as well as explaining the interaction mechanisms among drugs.