Potential energy landscapes identify the information-theoretic nature of the epigenome

Garrett Jenkinson; Elisabet Pujadas; John Goutsias; Andrew P. Feinberg

doi:10.1038/ng.3811

Potential energy landscapes identify the information-theoretic nature of the epigenome

Garrett Jenkinson
, Elisabet Pujadas
, John Goutsias
, Andrew P. Feinberg

School of Medicine

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

Epigenetics is the study of biochemical modifications carrying information independent of DNA sequence, which are heritable through cell division. In 1940, Waddington coined the term "epigenetic landscape" as a metaphor for pluripotency and differentiation, but methylation landscapes have not yet been rigorously computed. Using principles from statistical physics and information theory, we derive epigenetic energy landscapes from whole-genome bisulfite sequencing (WGBS) data that enable us to quantify methylation stochasticity genome-wide using Shannon's entropy, associating it with chromatin structure. Moreover, we consider the Jensen-Shannon distance between sample-specific energy landscapes as a measure of epigenetic dissimilarity and demonstrate its effectiveness for discerning epigenetic differences. By viewing methylation maintenance as a communications system, we introduce methylation channels and show that higher-order chromatin organization can be predicted from their informational properties. Our results provide a fundamental understanding of the information-theoretic nature of the epigenome that leads to a powerful approach for studying its role in disease and aging.

Original language	English (US)
Pages (from-to)	719-729
Number of pages	11
Journal	Nature genetics
Volume	49
Issue number	5
DOIs	https://doi.org/10.1038/ng.3811
State	Published - May 1 2017

ASJC Scopus subject areas

Genetics

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10.1038/ng.3811

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@article{94ee0315f066431ea429621ec49d1e4e,

title = "Potential energy landscapes identify the information-theoretic nature of the epigenome",

abstract = "Epigenetics is the study of biochemical modifications carrying information independent of DNA sequence, which are heritable through cell division. In 1940, Waddington coined the term {"}epigenetic landscape{"} as a metaphor for pluripotency and differentiation, but methylation landscapes have not yet been rigorously computed. Using principles from statistical physics and information theory, we derive epigenetic energy landscapes from whole-genome bisulfite sequencing (WGBS) data that enable us to quantify methylation stochasticity genome-wide using Shannon's entropy, associating it with chromatin structure. Moreover, we consider the Jensen-Shannon distance between sample-specific energy landscapes as a measure of epigenetic dissimilarity and demonstrate its effectiveness for discerning epigenetic differences. By viewing methylation maintenance as a communications system, we introduce methylation channels and show that higher-order chromatin organization can be predicted from their informational properties. Our results provide a fundamental understanding of the information-theoretic nature of the epigenome that leads to a powerful approach for studying its role in disease and aging.",

author = "Garrett Jenkinson and Elisabet Pujadas and John Goutsias and Feinberg, \{Andrew P.\}",

note = "Funding Information: We thank X. Li, A. Vandiver, and J. Walston (Johns Hopkins University) for cells and/or FASTQ files; R. Trygvadottir, B. Berndsen, A. Idrizi, and C. Callahan (Johns Hopkins University) for sequencing; J.-P. Fortin and K. Hansen for providing A and B compartment data; I. Morrison (University of Otago) and A. Gimelbrant (Dana-Farber Cancer Institute) for access to imprinted gene and MAE data sets; A. Meissner and M. Ziller (Broad Institute) for access to bisulfite sequencing data sets; and W. Timp and K. Hansen (Johns Hopkins University) for critical reading of the manuscript. This work was supported by US National Institutes of Health (NIH) grants R01CA054358 and DP1ES022579 to A.P.F., National Science Foundation grants CCF-1217213 and CCF-1656201 to J.G., and NIH grant AG021334 to J. Walston. E.P. was supported by the Medical Scientist Training Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2017 Nature America, Inc., part of Springer Nature. All rights reserved.",

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N2 - Epigenetics is the study of biochemical modifications carrying information independent of DNA sequence, which are heritable through cell division. In 1940, Waddington coined the term "epigenetic landscape" as a metaphor for pluripotency and differentiation, but methylation landscapes have not yet been rigorously computed. Using principles from statistical physics and information theory, we derive epigenetic energy landscapes from whole-genome bisulfite sequencing (WGBS) data that enable us to quantify methylation stochasticity genome-wide using Shannon's entropy, associating it with chromatin structure. Moreover, we consider the Jensen-Shannon distance between sample-specific energy landscapes as a measure of epigenetic dissimilarity and demonstrate its effectiveness for discerning epigenetic differences. By viewing methylation maintenance as a communications system, we introduce methylation channels and show that higher-order chromatin organization can be predicted from their informational properties. Our results provide a fundamental understanding of the information-theoretic nature of the epigenome that leads to a powerful approach for studying its role in disease and aging.

AB - Epigenetics is the study of biochemical modifications carrying information independent of DNA sequence, which are heritable through cell division. In 1940, Waddington coined the term "epigenetic landscape" as a metaphor for pluripotency and differentiation, but methylation landscapes have not yet been rigorously computed. Using principles from statistical physics and information theory, we derive epigenetic energy landscapes from whole-genome bisulfite sequencing (WGBS) data that enable us to quantify methylation stochasticity genome-wide using Shannon's entropy, associating it with chromatin structure. Moreover, we consider the Jensen-Shannon distance between sample-specific energy landscapes as a measure of epigenetic dissimilarity and demonstrate its effectiveness for discerning epigenetic differences. By viewing methylation maintenance as a communications system, we introduce methylation channels and show that higher-order chromatin organization can be predicted from their informational properties. Our results provide a fundamental understanding of the information-theoretic nature of the epigenome that leads to a powerful approach for studying its role in disease and aging.

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Potential energy landscapes identify the information-theoretic nature of the epigenome

Abstract

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