Hierarchy and control of ageing-related methylation networks.

DNA methylation provides one of the most widely studied biomarkers of ageing. Since the methylation of CpG dinucleotides function as switches in cellular mechanisms, it is plausible to assume that by proper adjustment of these switches age may be tuned. Though, adjusting hundreds of CpG methylation...

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Autores principales:	Gergely Palla, Péter Pollner, Judit Börcsök, András Major, Béla Molnár, István Csabai
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d8647e82189440069e36fb450814d62f
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spelling	oai:doaj.org-article:d8647e82189440069e36fb450814d62f2021-12-02T19:57:46ZHierarchy and control of ageing-related methylation networks.1553-734X1553-735810.1371/journal.pcbi.1009327https://doaj.org/article/d8647e82189440069e36fb450814d62f2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009327https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358DNA methylation provides one of the most widely studied biomarkers of ageing. Since the methylation of CpG dinucleotides function as switches in cellular mechanisms, it is plausible to assume that by proper adjustment of these switches age may be tuned. Though, adjusting hundreds of CpG methylation levels coherently may never be feasible and changing just a few positions may lead to biologically unstable state. A prominent example of methylation-based age estimators is provided by Horvath's clock, based on 353 CpG dinucleotides, showing a high correlation (not necessarily causation) with chronological age across multiple tissue types. On this small subset of CpG dinucleotides we demonstrate how the adjustment of one methylation level leads to a cascade of changes at other sites. Among the studied subset, we locate the most important CpGs (and related genes) that may have a large influence on the rest of the sub-system. According to our analysis, the structure of this network is way more hierarchical compared to what one would expect based on ensembles of uncorrelated connections. Therefore, only a handful of CpGs is enough to modify the system towards a desired state. When propagation of the change over the network is taken into account, the resulting modification in the predicted age can be significantly larger compared to the effect of isolated CpG perturbations. By adjusting the most influential single CpG site and following the propagation of methylation level changes we can reach up to 5.74 years in virtual age reduction, significantly larger than without taking into account of the network control. Extending our approach to the whole methylation network may identify key nodes that have controller role in the ageing process.Gergely PallaPéter PollnerJudit BörcsökAndrás MajorBéla MolnárIstván CsabaiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 9, p e1009327 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Gergely Palla Péter Pollner Judit Börcsök András Major Béla Molnár István Csabai Hierarchy and control of ageing-related methylation networks.
description	DNA methylation provides one of the most widely studied biomarkers of ageing. Since the methylation of CpG dinucleotides function as switches in cellular mechanisms, it is plausible to assume that by proper adjustment of these switches age may be tuned. Though, adjusting hundreds of CpG methylation levels coherently may never be feasible and changing just a few positions may lead to biologically unstable state. A prominent example of methylation-based age estimators is provided by Horvath's clock, based on 353 CpG dinucleotides, showing a high correlation (not necessarily causation) with chronological age across multiple tissue types. On this small subset of CpG dinucleotides we demonstrate how the adjustment of one methylation level leads to a cascade of changes at other sites. Among the studied subset, we locate the most important CpGs (and related genes) that may have a large influence on the rest of the sub-system. According to our analysis, the structure of this network is way more hierarchical compared to what one would expect based on ensembles of uncorrelated connections. Therefore, only a handful of CpGs is enough to modify the system towards a desired state. When propagation of the change over the network is taken into account, the resulting modification in the predicted age can be significantly larger compared to the effect of isolated CpG perturbations. By adjusting the most influential single CpG site and following the propagation of methylation level changes we can reach up to 5.74 years in virtual age reduction, significantly larger than without taking into account of the network control. Extending our approach to the whole methylation network may identify key nodes that have controller role in the ageing process.
format	article
author	Gergely Palla Péter Pollner Judit Börcsök András Major Béla Molnár István Csabai
author_facet	Gergely Palla Péter Pollner Judit Börcsök András Major Béla Molnár István Csabai
author_sort	Gergely Palla
title	Hierarchy and control of ageing-related methylation networks.
title_short	Hierarchy and control of ageing-related methylation networks.
title_full	Hierarchy and control of ageing-related methylation networks.
title_fullStr	Hierarchy and control of ageing-related methylation networks.
title_full_unstemmed	Hierarchy and control of ageing-related methylation networks.
title_sort	hierarchy and control of ageing-related methylation networks.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d8647e82189440069e36fb450814d62f
work_keys_str_mv	AT gergelypalla hierarchyandcontrolofageingrelatedmethylationnetworks AT peterpollner hierarchyandcontrolofageingrelatedmethylationnetworks AT juditborcsok hierarchyandcontrolofageingrelatedmethylationnetworks AT andrasmajor hierarchyandcontrolofageingrelatedmethylationnetworks AT belamolnar hierarchyandcontrolofageingrelatedmethylationnetworks AT istvancsabai hierarchyandcontrolofageingrelatedmethylationnetworks
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Hierarchy and control of ageing-related methylation networks.

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