Genome-Anchored Foundation Model Embeddings Improve Molecular Prediction from Histology Images

Precision oncology requires accurate molecular insights, yet obtaining these directly from genomics is costly and time-consuming for broad clinical use. Predicting complex molecular features and patient prognosis directly from routine whole-slide images (WSI) remains a major challenge for current deep learning methods. Here we introduce PathLUPI, which uses transcriptomic privileged information during training to extract genome-anchored histological embeddings, enabling effective molecular prediction using only WSIs at inference. Through extensive evaluation across 49 molecular oncology tasks using 11,257 cases among 20 cohorts, PathLUPI demonstrated superior performance compared to conventional methods trained solely on WSIs. Crucially, it achieves AUC $\geq$ 0.80 in 14 of the biomarker prediction and molecular subtyping tasks and C-index $\geq$ 0.70 in survival cohorts of 5 major cancer types. Moreover, PathLUPI embeddings reveal distinct cellular morphological signatures associated with specific genotypes and related biological pathways within WSIs. By effectively encoding molecular context to refine WSI representations, PathLUPI overcomes a key limitation of existing models and offers a novel strategy to bridge molecular insights with routine pathology workflows for wider clinical application.

A4-Unet: Deformable Multi-Scale Attention Network for Brain Tumor Segmentation

Brain tumor segmentation models have aided diagnosis in recent years. However, they face MRI complexity and variability challenges, including irregular shapes and unclear boundaries, leading to noise, misclassification, and incomplete segmentation, thereby limiting accuracy. To address these issues, we adhere to an outstanding Convolutional Neural Networks (CNNs) design paradigm and propose a novel network named A4-Unet. In A4-Unet, Deformable Large Kernel Attention (DLKA) is incorporated in the encoder, allowing for improved capture of multi-scale tumors. Swin Spatial Pyramid Pooling (SSPP) with cross-channel attention is employed in a bottleneck further to study long-distance dependencies within images and channel relationships. To enhance accuracy, a Combined Attention Module (CAM) with Discrete Cosine Transform (DCT) orthogonality for channel weighting and convolutional element-wise multiplication is introduced for spatial weighting in the decoder. Attention gates (AG) are added in the skip connection to highlight the foreground while suppressing irrelevant background information. The proposed network is evaluated on three authoritative MRI brain tumor benchmarks and a proprietary dataset, and it achieves a 94.4% Dice score on the BraTS 2020 dataset, thereby establishing multiple new state-of-the-art benchmarks. The code is available here: https://github.com/WendyWAAAAANG/A4-Unet.