Jia Wu

Jiameng Chen, Xiantao Cai, Jia Wu et al.

Antibody design remains a critical challenge in therapeutic and diagnostic development, particularly for complex antigens with diverse binding interfaces. Current computational methods face two main limitations: (1) capturing geometric features while preserving symmetries, and (2) generalizing novel antigen interfaces. Despite recent advancements, these methods often fail to accurately capture molecular interactions and maintain structural integrity. To address these challenges, we propose \textbf{AbMEGD}, an end-to-end framework integrating \textbf{M}ulti-scale \textbf{E}quivariant \textbf{G}raph \textbf{D}iffusion for antibody sequence and structure co-design. Leveraging advanced geometric deep learning, AbMEGD combines atomic-level geometric features with residue-level embeddings, capturing local atomic details and global sequence-structure interactions. Its E(3)-equivariant diffusion method ensures geometric precision, computational efficiency, and robust generalizability for complex antigens. Furthermore, experiments using the SAbDab database demonstrate a 10.13\% increase in amino acid recovery, 3.32\% rise in improvement percentage, and a 0.062~Å reduction in root mean square deviation within the critical CDR-H3 region compared to DiffAb, a leading antibody design model. These results highlight AbMEGD's ability to balance structural integrity with improved functionality, establishing a new benchmark for sequence-structure co-design and affinity optimization. The code is available at: https://github.com/Patrick221215/AbMEGD.

Pingjun Chen, Muhammad Aminu, Siba El Hussein et al.

The cells and their spatial patterns in the tumor microenvironment (TME) play a key role in tumor evolution, and yet the latter remains an understudied topic in computational pathology. This study, to the best of our knowledge, is among the first to hybridize local and global graph methods to profile orchestration and interaction of cellular components. To address the challenge in hematolymphoid cancers, where the cell classes in TME may be unclear, we first implemented cell-level unsupervised learning and identified two new cell subtypes. Local cell graphs or supercells were built for each image by considering the individual cell's geospatial location and classes. Then, we applied supercell level clustering and identified two new cell communities. In the end, we built global graphs to abstract spatial interaction patterns and extract features for disease diagnosis. We evaluate the proposed algorithm on H&E slides of 60 hematolymphoid neoplasms and further compared it with three cell level graph-based algorithms, including the global cell graph, cluster cell graph, and FLocK. The proposed algorithm achieved a mean diagnosis accuracy of 0.703 with the repeated 5-fold cross-validation scheme. In conclusion, our algorithm shows superior performance over the existing methods and can be potentially applied to other cancer types.

Stephen Baek, Yusen He, Bryan G. Allen et al.

Non-small-cell lung cancer (NSCLC) represents approximately 80-85% of lung cancer diagnoses and is the leading cause of cancer-related death worldwide. Recent studies indicate that image-based radiomics features from positron emission tomography-computed tomography (PET/CT) images have predictive power on NSCLC outcomes. To this end, easily calculated functional features such as the maximum and the mean of standard uptake value (SUV) and total lesion glycolysis (TLG) are most commonly used for NSCLC prognostication, but their prognostic value remains controversial. Meanwhile, convolutional neural networks (CNN) are rapidly emerging as a new premise for cancer image analysis, with significantly enhanced predictive power compared to other hand-crafted radiomics features. Here we show that CNN trained to perform the tumor segmentation task, with no other information than physician contours, identify a rich set of survival-related image features with remarkable prognostic value. In a retrospective study on 96 NSCLC patients before stereotactic-body radiotherapy (SBRT), we found that the CNN segmentation algorithm (U-Net) trained for tumor segmentation in PET/CT images, contained features having strong correlation with 2- and 5-year overall and disease-specific survivals. The U-net algorithm has not seen any other clinical information (e.g. survival, age, smoking history) than the images and the corresponding tumor contours provided by physicians. Furthermore, through visualization of the U-Net, we also found convincing evidence that the regions of progression appear to match with the regions where the U-Net features identified patterns that predicted higher likelihood of death. We anticipate our findings will be a starting point for more sophisticated non-intrusive patient specific cancer prognosis determination.