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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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. |
format | Online Article Text |
id | pubmed-9795372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sethianurag jointinferenceofphysiologicalnetworkandsurvivalanalysisidentifiesfactorsassociatedwithagingrate AT melamudeugene jointinferenceofphysiologicalnetworkandsurvivalanalysisidentifiesfactorsassociatedwithagingrate |