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