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.
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Garrett
authors.initials: G
authors.lastname: Jenkinson
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Pujadas
authors.affiliation: Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: John
authors.initials: J
authors.lastname: Goutsias
authors.affiliation: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA.|Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D000375:Aging / Q000235:genetics; D000465:Algorithms; D002478:Cells, Cultured; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism; D019277:Entropy; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods*; D013447:Sulfites / Q000737:chemistry
chemical_list: D013447:Sulfites; C042345:hydrogen sulfite