The methodology, validated with international reference samples such as those from the Genome in a Bottle (GIAB) consortium and the U.S. National Institute of Standards and Technology (NIST), allows for the generation of complete human methylomes with adequate quality. Initial results from 2026 indicate a global sequencing coverage of approximately 10×, providing information on up to 27 million CpG positions distributed across the human genome. This resolution significantly surpasses that of methylation microarrays or capture experiments.
DNA methylation, an epigenetic modification that does not alter the DNA sequence but regulates gene expression, involves the addition of a methyl group to specific cytosines (5-methylcytosine or 5mC). The Illumina 5-Base DNA Prep assay uses a selective enzymatic conversion of methylated cytosines to thymines, better preserving DNA integrity and the complexity of nucleic acid libraries compared to traditional bisulfite treatment. Subsequent bioinformatic analysis reconstructs the five bases: adenine, thymine, guanine, cytosine, and 5-methylcytosine.
A key advantage of this technology is its ability to obtain both the complete genome sequence and the complete methylome profile from a single nucleic acid library preparation and sequencing experiment. This facilitates the joint study of genetic variants and epigenetic changes, integrating two complementary levels of biological information.
The combined analysis of genome and methylome opens new avenues in biomedical research, including the identification of biomarkers for disease development, progression, and prognosis. Its applications encompass the study of complex diseases, molecular characterization of tumors, identification of epigenetic signatures, analysis of treatment response, and longitudinal patient monitoring.
The technology is particularly relevant for studies on biological aging. Epigenetic clocks, which use methylation patterns to estimate epigenetic age, will benefit from this near-complete genomic information. It will enable not only the application and comparison of existing clocks but also the development of new models and the identification of molecular mechanisms associated with aging and age-related diseases.
This advancement was made possible through co-financing from the Island Department of Research, Innovation, and Development of the Cabildo de Tenerife, via the Master Plan for Innovation of the island of Tenerife, during the period between 2025 and the first half of 2026.
