Interpretable deep clustering survival machines for Alzheimer’s disease subtype discovery

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder that has impacted millions of people worldwide. The neuroanatomical heterogeneity of AD has made it challenging to fully understand the disease mechanism. Identifying AD subtypes during the prodromal stage and determining their genetic basis would be immensely valuable for drug discovery and subsequent clinical treatment. Previous studies that clustered subgroups typically used unsupervised learning techniques, neglecting the survival information and potentially limiting the insights gained. To address this problem, we propose an interpretable survival analysis method called Deep Clustering Survival Machines (DCSM), which combines both discriminative and generative mechanisms. Similar to mixture models, we assume that the timing information of survival data can be generatively described by a mixture of parametric distributions, referred to as expert distributions. We learn the weights of these expert distributions for individual instances in a discriminative manner by leveraging their features. This allows us to characterize the survival information of each instance through a weighted combination of the learned expert distributions. We demonstrate the superiority of the DCSM method by applying this approach to cluster patients with mild cognitive impairment (MCI) into subgroups with different risks of converting to AD. Conventional clustering measurements for survival analysis along with genetic association studies successfully validate the effectiveness of the proposed method and characterize our clustering findings.