s-SuStaIn: Scaling subtype and stage inference via simultaneous clustering of subjects and biomarkers.

Abstract

Event-based models (EBM) provide an important platform for modeling disease progression. This work successfully extends previous EBM approaches to work with larger sets of biomarkers while simultaneously modeling heterogeneity in disease progression trajectories. We develop and validate the s-SuStain method for scalable event-based modeling of disease progression subtypes using large numbers of features. s-SuStaIn is typically an order of magnitude faster than its predecessor (SuStaIn). Moreover, we perform a case study with s-SuStaIn using open access cross-sectional Alzheimer's Disease Neuroimaging (ADNI) data to stage AD patients into four subtypes based on dynamic disease progression. s-SuStaIn shows that the inferred subtypes and stages predict progression to AD among MCI subjects. The subtypes show difference in AD incidence-rates and reveal clinically meaningful progression trajectories when mapped to a brain atlas.