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Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales

The epigenetic trajectory of DNA methylation profiles has a nonlinear relationship with time, reflecting rapid changes in DNA methylation early in life that progressively slow with age. In this study, we use pseudotime analysis to determine the functional form of these trajectories. Unlike epigeneti...

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Detalles Bibliográficos
Autores principales: Lapborisuth, Kalsuda, Farrell, Colin, Pellegrini, Matteo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909670/
https://www.ncbi.nlm.nih.gov/pubmed/35269389
http://dx.doi.org/10.3390/cells11050767
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author Lapborisuth, Kalsuda
Farrell, Colin
Pellegrini, Matteo
author_facet Lapborisuth, Kalsuda
Farrell, Colin
Pellegrini, Matteo
author_sort Lapborisuth, Kalsuda
collection PubMed
description The epigenetic trajectory of DNA methylation profiles has a nonlinear relationship with time, reflecting rapid changes in DNA methylation early in life that progressively slow with age. In this study, we use pseudotime analysis to determine the functional form of these trajectories. Unlike epigenetic clocks that constrain the functional form of methylation changes with time, pseudotime analysis orders samples along a path, based on similarities in a latent dimension, to provide an unbiased trajectory. We show that pseudotime analysis can be applied to DNA methylation in human blood and brain tissue and find that it is highly correlated with the epigenetic states described by the Epigenetic Pacemaker. Moreover, we show that the pseudotime trajectory can be modeled with respect to time, using a sum of two exponentials, with coefficients that are close to the timescales of human age-associated mortality. Thus, for the first time, we can identify age-associated molecular changes that appear to track the exponential dynamics of mortality risk.
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spelling pubmed-89096702022-03-11 Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales Lapborisuth, Kalsuda Farrell, Colin Pellegrini, Matteo Cells Article The epigenetic trajectory of DNA methylation profiles has a nonlinear relationship with time, reflecting rapid changes in DNA methylation early in life that progressively slow with age. In this study, we use pseudotime analysis to determine the functional form of these trajectories. Unlike epigenetic clocks that constrain the functional form of methylation changes with time, pseudotime analysis orders samples along a path, based on similarities in a latent dimension, to provide an unbiased trajectory. We show that pseudotime analysis can be applied to DNA methylation in human blood and brain tissue and find that it is highly correlated with the epigenetic states described by the Epigenetic Pacemaker. Moreover, we show that the pseudotime trajectory can be modeled with respect to time, using a sum of two exponentials, with coefficients that are close to the timescales of human age-associated mortality. Thus, for the first time, we can identify age-associated molecular changes that appear to track the exponential dynamics of mortality risk. MDPI 2022-02-22 /pmc/articles/PMC8909670/ /pubmed/35269389 http://dx.doi.org/10.3390/cells11050767 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lapborisuth, Kalsuda
Farrell, Colin
Pellegrini, Matteo
Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales
title Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales
title_full Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales
title_fullStr Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales
title_full_unstemmed Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales
title_short Pseudotime Analysis Reveals Exponential Trends in DNA Methylation Aging with Mortality Associated Timescales
title_sort pseudotime analysis reveals exponential trends in dna methylation aging with mortality associated timescales
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909670/
https://www.ncbi.nlm.nih.gov/pubmed/35269389
http://dx.doi.org/10.3390/cells11050767
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