Unsupervised learning of disease subtypes from continuous time Hidden Markov Models of disease progression

Abstract

The detection of subtypes of complex diseases has important implications for diagnosis and treatment. Numerous prior studies have used data-driven approaches to identify clusters of similar patients, but it is not yet clear how to best specify what constitutes a clinically meaningful phenotype. This study explored disease subtyping on the basis of temporal development patterns. In particular, we attempted to differentiate infants with autism spectrum disorder into more fine-grained classes with distinctive patterns of early skill development. We modeled the progression of autism explicitly using a continuous-time hidden Markov model. Subsequently, we compared subjects on the basis of their trajectories through the model state space. Two approaches to subtyping were utilized, one based on time-series clustering with a custom distance function and one based on tensor factorization. A web application was also developed to facilitate the visual exploration of our results. Results suggested the presence of 3 developmental subgroups in the ASD outcome group. The two subtyping approaches are contrasted and possible future directions for research are discussed.