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Unscrambling disease progression at scale: fast inference of event permutations with optimal transport

Wijeratne, PA; Alexander, DC; (2024) Unscrambling disease progression at scale: fast inference of event permutations with optimal transport. In: Advances in Neural Information Processing Systems. NeurIPS Green open access

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Abstract

Disease progression models infer group-level temporal trajectories of change in patients' features as a chronic degenerative condition plays out. They provide unique insight into disease biology and staging systems with individual-level clinical utility. Discrete models consider disease progression as a latent permutation of events, where each event corresponds to a feature becoming measurably abnormal. However, permutation inference using traditional maximum likelihood approaches becomes prohibitive due to combinatoric explosion, severely limiting model dimensionality and utility. Here we leverage ideas from optimal transport to model disease progression as a latent permutation matrix of events belonging to the Birkhoff polytope, facilitating fast inference via optimisation of the variational lower bound. This enables a factor of 1000 times faster inference than the current state of the art and, correspondingly, supports models with several orders of magnitude more features than the current state of the art can consider. Experiments demonstrate the increase in speed, accuracy and robustness to noise in simulation. Further experiments with real-world imaging data from two separate datasets, one from Alzheimer's disease patients, the other age-related macular degeneration, showcase, for the first time, pixel-level disease progression events in the brain and eye, respectively. Our method is low compute, interpretable and applicable to any progressive condition and data modality, giving it broad potential clinical utility.

Type: Proceedings paper
Title: Unscrambling disease progression at scale: fast inference of event permutations with optimal transport
Event: NeurIPS 2024
Open access status: An open access version is available from UCL Discovery
Publisher version: https://proceedings.neurips.cc/paper_files/paper/2...
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10207246
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