Longitudinal personal DNA methylome dynamics in a human with a chronic condition

Area of Science:

• Integrative 'omics' analysis in human health
• Personalized epigenetics and transcriptomics

Background:

• Epigenomics, particularly DNA methylation, plays a crucial role in gene regulation and precision health.
• Environmental and lifestyle factors significantly influence epigenetic modifications.
• Understanding longitudinal 'omics' changes in individuals is key to deciphering health dynamics.

Purpose of the Study:

• To profile whole-genome DNA methylation and transcriptome longitudinally over 36 months in a single human subject.
• To investigate the association between epigenomic and transcriptomic changes with physiological events.
• To identify long-term epigenetic patterns and their relation to gene regulation.

Main Methods:

• Collected peripheral blood mononuclear cells from a human volunteer over 36 months.
• Generated 28 whole-genome DNA methylome and 57 transcriptome datasets.
• Analyzed longitudinal data for associations between 'omics' profiles and physiological changes, including glucose levels and infections.

Main Results:

• DNA methylomic changes were linked to infrequent glucose level alterations, with shifts often preceding detectable elevation by 80-90 days.
• The transcriptome showed dynamic changes during acute events, such as viral infections.
• Deep personal methylome analysis revealed numerous stable, longitudinally consistent allelic differentially methylated regions associated with allele-specific gene regulation.

Conclusions:

• Longitudinal DNA methylation patterns correlate with chronic physiological conditions, such as glucose metabolism.
• Transcriptomic dynamics reflect acute physiological events, like infections.
• This study demonstrates the distinct roles of DNA methylation and transcriptome in reflecting chronic versus acute physiological changes in an individual.