Disease2Vec: Encoding Alzheimer’s progression via disease embedding tree

For decades, a variety of predictive approaches have been proposed and evaluated in terms of their prediction capability for Alzheimer's Disease (AD) and its precursor - mild cognitive impairment (MCI). Most of them focused on prediction or identification of statistical differences among different clinical groups or phases, especially in the context of binary or multi-class classification. The continuous nature of AD development and transition states between successive AD related stages have been typically overlooked. Though a few progression models of AD have been studied recently, they were mainly designed to determine and compare the order of specific biomarkers. How to effectively predict the individual patient's status within a wide spectrum of continuous AD progression has been largely understudied. In this work, we developed a novel learning-based embedding framework to encode the intrinsic relations among AD related clinical stages by a set of meaningful embedding vectors in the latent space (Disease2Vec). We named this process as disease embedding. By Disease2Vec, our framework generates a disease embedding tree (DETree) which effectively represents different clinical stages as a tree trajectory reflecting AD progression and thus can be used to predict clinical status by projecting individuals onto this continuous trajectory. Through this model, DETree can not only perform efficient and accurate prediction for patients at any stages of AD development (across five fine-grained clinical groups instead of typical two groups), but also provide richer status information by examining the projecting locations within a wide and continuous AD progression process. (Code will be available: https://github.com/qidianzl/Disease2Vec.).