An effective encoding of human medical conditions in disease space provides a versatile framework for deciphering disease associations.

It is challenging to identify comorbidity patterns and mechanistically investigate disease associations based on health-related data that are often sparse, large-scale, and multimodal. Adopting a systems biology approach, embedding-based algorithms provide a new perspective to examine diseases under a unified framework by mapping diseases into a high-dimensional space as embedding vectors. These vectors and their constituted disease space encode pathological information and enable a quantitative and systemic measurement of the similarity between any pair of diseases, opening up an avenue for numerous types of downstream analyses. Here, we exemplify its potential through applications in discovering hidden disease associations, assisting in genetic parameter estimation, facilitating data-driven disease classifications, and transforming genetic association studies of diseases in consideration of comorbidities. While underscoring the power and versatility of this approach, we also discuss the challenges posed by medical context, requirements of online training and result validation, and research opportunities in constructing foundation models from multimodal disease data. With continued innovation and exploration, disease embedding has the potential to transform the fields of disease association analysis and even pathology studies by providing a holistic representation of patient health status.