Survival prediction is a significant challenge in cancer management. Tumor micro-environment is a highly sophisticated ecosystem consisting of cancer cells, immune cells, endothelial cells, fibroblasts, nerves and extracellular matrix. However, current methods often neglect the fact that the contribution to prognosis differs with tissue types. In this paper, we propose ProtoSurv, a novel heterogeneous graph model for WSI survival prediction. The learning process of ProtoSurv is not only driven by data but also incorporates pathological domain knowledge, including the awareness of tissue heterogeneity, the emphasis on prior knowledge of prognostic-related tissues, and the depiction of spatial interaction across multiple tissues.

Predicting genetic perturbations enables the identification of potentially crucial genes prior to wet-lab experiments, significantly improving overall experimental efficiency. Since genes are the foundation of cellular life, building gene regulatory networks (GRN) is essential to understand and predict the effects of genetic perturbations. However, current methods fail to fully leverage gene-related information, and solely rely on simple evaluation metrics to construct coarse-grained GRN. More importantly, they ignore functional differences between biotypes, limiting the ability to capture potential gene interactions. In this work, we leverage pre-trained large language model and DNA sequence model to extract features from gene descriptions and DNA sequence data, respectively, which serve as the initialization for gene representations. Additionally, we introduce gene biotype information for the first time in genetic perturbation, simulating the distinct roles of genes with different biotypes in regulating cellular processes, while capturing implicit gene relationships through graph structure learning (GSL). We propose GRAPE, a heterogeneous graph neural network (HGNN) that leverages gene representations initialized with features from descriptions and sequences, models the distinct roles of genes with different biotypes, and dynamically refines the GRN through GSL. The results on publicly available datasets show that our method achieves state-of-the-art performance. The code for reproducing the results can be seen at the anonymous link: https://anonymous.4open.science/r/GRAPE-EB39.