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Interpretable machine learning for high-dimensional trajectories of aging health

Farrell, Spencer, Mitnitski, Arnold, Rockwood, Kenneth, Rutenberg, Andrew D.·2022·PLOS Computational Biology

Abstract

We have built a computational model for individual aging trajectories of health and survival, which contains physical, functional, and biological variables, and is conditioned on demographic, lifestyle, and medical background information. We combine techniques of modern machine learning with an interpretable interaction network, where health variables are coupled by explicit pair-wise interactions within a stochastic dynamical system. Our dynamic joint interpretable network (DJIN) model is scalable to large longitudinal data sets, is predictive of individual high-dimensional health trajectories and survival from baseline health states, and infers an interpretable network of directed interactions between the health variables. The network identifies plausible physiological connections between health variables as well as clusters of strongly connected health variables. We use English Longitudinal Study of Aging (ELSA) data to train our model and show that it performs better than multiple dedicated linear models for health outcomes and survival. We compare our model with flexible lower-dimensional latent-space models to explore the dimensionality required to accurately model aging health outcomes. Our DJIN model can be used to generate synthetic individuals that age realistically, to impute missing data, and to simulate future aging outcomes given arbitrary initial health states.

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  • A one-dimensional representation of the complex biochemistry and phenotypes of aging is supported by analyses of aging data.

    “The possibility of such a one-dimensional representation of the complex biochemistry and phenotypes of aging21–25 is supported by analyses of aging data26–30.”

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Metadata

Authors
Farrell, S., Mitnitski, A., Rockwood, K., & Rutenberg, A. D.
Venue
PLOS Computational Biology
Published
2022-01-10
Volume
18
Issue
1
Pages
e1009746
ISSN
1553-7358
Cited by
22
References
6
Language
en
Funders
  • Natural Sciences and Engineering Research Council of Canada (RGPIN 2019-05888)
  • Canadian Institutes of Health Research (PJT-156114)
  • Dalhousie Medical Research Foundation

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