arXiv subjects

Saisai Ding

Publications and source records attributed to Saisai Ding.

5 recordsLinked to original sources

arXiv2026

De novo design of protein binders targeting the human sweet taste receptor as potential sweet proteins

Excessive consumption of dietary sugars is a major contributor to metabolic disorders, driving global interest in finding alternative sweeteners with reduced caloric impact. Natural sweet proteins, such as brazzein, offer exceptional sweetness intensity with little caloric contribution. However, their widespread use is limited by restricted natural diversity, low stability, and high production costs. Recent advances in structural biology and de novo protein design provide new opportunities to overcome these limitations through rational engineering. In this study, we report an integrated computational pipeline for the de novo design of protein binders targeting the human sweet taste receptor subunit TAS1R2, a key component of the heterodimeric class C G protein-coupled receptor mediating sweetness perception. The workflow combines diffusion-based backbone generation (RFdiffusion), neural network-guided sequence design (ProteinMPNN), structure-based filtering using Boltz-1, and binding energy evaluation via MM/GBSA calculations. Using the recently resolved cryo-EM structure of the TAS1R2 receptor, protein binders were designed to target both the Venus Flytrap Domain and the cysteine-rich domain of TAS1R2. A few designed binders exhibited favorable structural confidence and predicted binding energetics. In particular, Binder2 exhibited brazzein-like structural plausibility through specific short-range CRD contacts, while Binder1 displayed the strongest predicted binding affinity. Structural analyses of the binder-receptor complex revealed distinct binding modes and secondary structure profiles among the designs. This study demonstrates the feasibility of de novo designing protein binders that emulate key functional properties of natural sweet proteins, establishing a computational framework for the rational development of next-generation protein-based sweeteners.

q-bio.BM↗

arXiv2025

Reconstruction and Prediction of Volterra Integral Equations Driven by Gaussian Noise

Integral equations are widely used in fields such as applied modeling, medical imaging, and system identification, providing a powerful framework for solving deterministic problems. While parameter identification for differential equations has been extensively studied, the focus on integral equations, particularly stochastic Volterra integral equations, remains limited. This research addresses the parameter identification problem, also known as the equation reconstruction problem, in Volterra integral equations driven by Gaussian noise. We propose an improved deep neural networks framework for estimating unknown parameters in the drift term of these equations. The network represents the primary variables and their integrals, enhancing parameter estimation accuracy by incorporating inter-output relationships into the loss function. Additionally, the framework extends beyond parameter identification to predict the system's behavior outside the integration interval. Prediction accuracy is validated by comparing predicted and true trajectories using a 95% confidence interval. Numerical experiments demonstrate the effectiveness of the proposed deep neural networks framework in both parameter identification and prediction tasks, showing robust performance under varying noise levels and providing accurate solutions for modeling stochastic systems.

stat.ML↗

arXiv2023

Multi-Scale Prototypical Transformer for Whole Slide Image Classification

Whole slide image (WSI) classification is an essential task in computational pathology. Despite the recent advances in multiple instance learning (MIL) for WSI classification, accurate classification of WSIs remains challenging due to the extreme imbalance between the positive and negative instances in bags, and the complicated pre-processing to fuse multi-scale information of WSI. To this end, we propose a novel multi-scale prototypical Transformer (MSPT) for WSI classification, which includes a prototypical Transformer (PT) module and a multi-scale feature fusion module (MFFM). The PT is developed to reduce redundant instances in bags by integrating prototypical learning into the Transformer architecture. It substitutes all instances with cluster prototypes, which are then re-calibrated through the self-attention mechanism of the Trans-former. Thereafter, an MFFM is proposed to fuse the clustered prototypes of different scales, which employs MLP-Mixer to enhance the information communication between prototypes. The experimental results on two public WSI datasets demonstrate that the proposed MSPT outperforms all the compared algorithms, suggesting its potential applications.

cs.CV↗

arXiv2023

Multi-scale Efficient Graph-Transformer for Whole Slide Image Classification

The multi-scale information among the whole slide images (WSIs) is essential for cancer diagnosis. Although the existing multi-scale vision Transformer has shown its effectiveness for learning multi-scale image representation, it still cannot work well on the gigapixel WSIs due to their extremely large image sizes. To this end, we propose a novel Multi-scale Efficient Graph-Transformer (MEGT) framework for WSI classification. The key idea of MEGT is to adopt two independent Efficient Graph-based Transformer (EGT) branches to process the low-resolution and high-resolution patch embeddings (i.e., tokens in a Transformer) of WSIs, respectively, and then fuse these tokens via a multi-scale feature fusion module (MFFM). Specifically, we design an EGT to efficiently learn the local-global information of patch tokens, which integrates the graph representation into Transformer to capture spatial-related information of WSIs. Meanwhile, we propose a novel MFFM to alleviate the semantic gap among different resolution patches during feature fusion, which creates a non-patch token for each branch as an agent to exchange information with another branch by cross-attention. In addition, to expedite network training, a novel token pruning module is developed in EGT to reduce the redundant tokens. Extensive experiments on TCGA-RCC and CAMELYON16 datasets demonstrate the effectiveness of the proposed MEGT.

cs.CV↗

arXiv2023

Pseudo-Data based Self-Supervised Federated Learning for Classification of Histopathological Images

Computer-aided diagnosis (CAD) can help pathologists improve diagnostic accuracy together with consistency and repeatability for cancers. However, the CAD models trained with the histopathological images only from a single center (hospital) generally suffer from the generalization problem due to the straining inconsistencies among different centers. In this work, we propose a pseudo-data based self-supervised federated learning (FL) framework, named SSL-FT-BT, to improve both the diagnostic accuracy and generalization of CAD models. Specifically, the pseudo histopathological images are generated from each center, which contains inherent and specific properties corresponding to the real images in this center, but does not include the privacy information. These pseudo images are then shared in the central server for self-supervised learning (SSL). A multi-task SSL is then designed to fully learn both the center-specific information and common inherent representation according to the data characteristics. Moreover, a novel Barlow Twins based FL (FL-BT) algorithm is proposed to improve the local training for the CAD model in each center by conducting contrastive learning, which benefits the optimization of the global model in the FL procedure. The experimental results on three public histopathological image datasets indicate the effectiveness of the proposed SSL-FL-BT on both diagnostic accuracy and generalization.

cs.CV↗