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Joint inference of physiological network and survival analysis identifies factors associated with aging rate

We describe methodology for joint reconstruction of physiological-survival networks from observational data capable of identifying key survival-associated variables, inferring a minimal physiological network structure, and bridging this network to the Gompertzian survival layer. Using synthetic netw...

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Detalles Bibliográficos
Autores principales: Sethi, Anurag, Melamud, Eugene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795372/
https://www.ncbi.nlm.nih.gov/pubmed/36590696
http://dx.doi.org/10.1016/j.crmeth.2022.100356
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author Sethi, Anurag
Melamud, Eugene
author_facet Sethi, Anurag
Melamud, Eugene
author_sort Sethi, Anurag
collection PubMed
description We describe methodology for joint reconstruction of physiological-survival networks from observational data capable of identifying key survival-associated variables, inferring a minimal physiological network structure, and bridging this network to the Gompertzian survival layer. Using synthetic network structures, we show that the method is capable of identifying aging variables in cohorts as small as 5,000 participants. Applying the methodology to the observational human cohort, we find that interleukin-6, vascular calcification, and red-blood distribution width are strong predictors of baseline fitness. More important, we find that red blood cell counts, kidney function, and phosphate level are directly linked to the Gompertzian aging rate. Our model therefore enables discovery of processes directly linked to the aging rate of our species. We further show that this epidemiological framework can be applied as a causal inference engine to simulate the effects of interventions on physiology and longevity.
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spelling pubmed-97953722022-12-29 Joint inference of physiological network and survival analysis identifies factors associated with aging rate Sethi, Anurag Melamud, Eugene Cell Rep Methods Article We describe methodology for joint reconstruction of physiological-survival networks from observational data capable of identifying key survival-associated variables, inferring a minimal physiological network structure, and bridging this network to the Gompertzian survival layer. Using synthetic network structures, we show that the method is capable of identifying aging variables in cohorts as small as 5,000 participants. Applying the methodology to the observational human cohort, we find that interleukin-6, vascular calcification, and red-blood distribution width are strong predictors of baseline fitness. More important, we find that red blood cell counts, kidney function, and phosphate level are directly linked to the Gompertzian aging rate. Our model therefore enables discovery of processes directly linked to the aging rate of our species. We further show that this epidemiological framework can be applied as a causal inference engine to simulate the effects of interventions on physiology and longevity. Elsevier 2022-12-02 /pmc/articles/PMC9795372/ /pubmed/36590696 http://dx.doi.org/10.1016/j.crmeth.2022.100356 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Sethi, Anurag
Melamud, Eugene
Joint inference of physiological network and survival analysis identifies factors associated with aging rate
title Joint inference of physiological network and survival analysis identifies factors associated with aging rate
title_full Joint inference of physiological network and survival analysis identifies factors associated with aging rate
title_fullStr Joint inference of physiological network and survival analysis identifies factors associated with aging rate
title_full_unstemmed Joint inference of physiological network and survival analysis identifies factors associated with aging rate
title_short Joint inference of physiological network and survival analysis identifies factors associated with aging rate
title_sort joint inference of physiological network and survival analysis identifies factors associated with aging rate
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795372/
https://www.ncbi.nlm.nih.gov/pubmed/36590696
http://dx.doi.org/10.1016/j.crmeth.2022.100356
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