Robust Multimodal Survival Prediction with the Latent Differentiation Conditional Variational AutoEncoder

The integrative analysis of histopathological images and genomic data has received increasing attention for survival prediction of human cancers. However, the existing studies always hold the assumption that full modalities are available. As a matter of fact, the cost for collecting genomic data is high, which sometimes makes genomic data unavailable in testing samples. A common way of tackling such incompleteness is to generate the genomic representations from the pathology images. Nevertheless, such strategy still faces the following two challenges: (1) The gigapixel whole slide images (WSIs) are huge and thus hard for representation. (2) It is difficult to generate the genomic embeddings with diverse function categories in a unified generative framework. To address the above challenges, we propose a Conditional Latent Differentiation Variational AutoEncoder (LD-CVAE) for robust multimodal survival prediction, even with missing genomic data. Specifically, a Variational Information Bottleneck Transformer (VIB-Trans) module is proposed to learn compressed pathological representations from the gigapixel WSIs. To generate different functional genomic features, we develop a novel Latent Differentiation Variational AutoEncoder (LD-VAE) to learn the common and specific posteriors for the genomic embeddings with diverse functions. Finally, we use the product-of-experts technique to integrate the genomic common posterior and image posterior for the joint latent distribution estimation in LD-CVAE. We test the effectiveness of our method on five different cancer datasets, and the experimental results demonstrate its superiority in both complete and missing modality scenarios.