Tianfan Fu

Designing enzymes with substrate-binding pockets is a critical challenge in protein engineering, as catalytic activity depends on the precise interaction between pockets and substrates. Currently, generative models dominate functional protein design but cannot model pocket-substrate interactions, which limits the generation of enzymes with precise catalytic environments. To address this issue, we propose EnzyPGM, a unified framework that jointly generates enzymes and substrate-binding pockets conditioned on functional priors and substrates, with a particular focus on learning accurate pocket-substrate interactions. At its core, EnzyPGM includes two main modules: a Residue-atom Bi-scale Attention (RBA) that jointly models intra-residue dependencies and fine-grained interactions between pocket residues and substrate atoms, and a Residue Function Fusion (RFF) that incorporates enzyme function priors into residue representations. Also, we curate EnzyPock, an enzyme-pocket dataset comprising 83,062 enzyme-substrate pairs across 1,036 four-level enzyme families. Extensive experiments demonstrate that EnzyPGM achieves state-of-the-art performance on EnzyPock. Notably, EnzyPGM reduces the average binding energy of 0.47 kcal/mol over EnzyGen, showing its superior performance on substrate-specific enzyme design. The code and dataset will be released later.

Clinical cystoscopy, the current standard for bladder cancer diagnosis, suffers from significant reliance on physician expertise, leading to variability and subjectivity in diagnostic outcomes. There is an urgent need for objective, accurate, and efficient computational approaches to improve bladder cancer diagnostics. Leveraging recent advancements in deep learning, this study proposes an integrated multi-task deep learning framework specifically designed for bladder cancer diagnosis from cystoscopic images. Our framework includes a robust classification model using EfficientNet-B0 enhanced with Convolutional Block Attention Module (CBAM), an advanced segmentation model based on ResNet34-UNet++ architecture with self-attention mechanisms and attention gating, and molecular subtyping using ConvNeXt-Tiny to classify molecular markers such as HER-2 and Ki-67. Additionally, we introduce a Gradio-based online diagnostic platform integrating all developed models, providing intuitive features including multi-format image uploads, bilingual interfaces, and dynamic threshold adjustments. Extensive experimentation demonstrates the effectiveness of our methods, achieving outstanding accuracy (93.28%), F1-score (82.05%), and AUC (96.41%) for classification tasks, and exceptional segmentation performance indicated by a Dice coefficient of 0.9091. The online platform significantly improved the accuracy, efficiency, and accessibility of clinical bladder cancer diagnostics, enabling practical and user-friendly deployment. The code is publicly available. Our multi-task framework and integrated online tool collectively advance the field of intelligent bladder cancer diagnosis by improving clinical reliability, supporting early tumor detection, and enabling real-time diagnostic feedback. These contributions mark a significant step toward AI-assisted decision-making in urology.