September 9, 2026
As part of our “Multiomics Explained” series, we’re unpacking one ome at a time. To get an overall picture, read our first piece, “What is multiomics? A simple guide to the future of biology.” You’ll learn how the omes work together to help solve some of the toughest questions in human health. To continue exploring, read about proteomics and transcriptomics. Now, let’s focus on defining epigenomics and how researchers are using it to advance biology, disease studies, and precision medicine.
While the genome is the blueprint for how cells and organisms function, the epigenome is the means by which that blueprint is read. The epigenome acts as a control panel, determining which genes are expressed without changing any DNA code. This ability to turn genes on and off gives the epigenome a critical role in biology.
Much like genomic changes, epigenomic variations can reveal disease. In some cases, these modifications happen even before genetic variations, which can provide an early warning signal to help detect approaching health issues.
What is the epigenome?
On the most fundamental level, the epigenome determines cell function. While almost every cell in the body has an identical genome, gene expression varies widely between muscle, skin, liver, brain, and every other cell type. The epigenome plays a major role in governing these variations.
Equally important, the epigenome acts as a type of thermostat, helping cells respond to environmental conditions, including air and water quality, diet, and exercise. For example, the epigenome in fat cells reacts to exercise, altering gene expression to adjust how those cells store energy and potentially burn it off.
Epigenetic changes are involved in aging, cancer, neurological conditions, and other diseases, making the epigenome a critical layer of information for uncovering disease mechanisms and discovering drug targets.
What epigenomics can tell us
Epigenomics studies key molecular players, called epigenetic tags, which act as molecular switches to either boost or reduce gene expression. One key epigenomic process is called DNA methylation, during which molecules (called methyl groups) attach to DNA to silence specific genes.
Another key mechanism is histone modification. If we stretched out the DNA from a single cell, it would measure around two meters. As a result, DNA must be packaged tightly to fit inside a cell’s nucleus. Protein complexes, called histones, help do the packaging, compacting chromosomes to fit into the available space. However, when a specific gene must be turned on, methyl and other epigenetic molecules loosen histones to enable expression.
Aberrant DNA methylation has been implicated in many diseases, including cancer, metabolic dysfunction, and neurodevelopmental disorders. By studying methylation and other epigenetic mechanisms, scientists can gain invaluable insights into how genes are regulated in complex diseases, discover diagnostic biomarkers, and potentially identify promising therapeutic targets.
How Illumina approaches epigenomics
Illumina has developed leading epigenetic technologies, including next-generation sequencing (NGS) and methylation microarrays, that enable genome-wide profiling of DNA methylation across diverse research applications. Illumina technologies have been foundational to epigenome-wide association studies (EWAS), which investigate associations between DNA methylation patterns and phenotypes, environmental exposures, and disease, providing insights into biological pathways and potential mechanisms underlying complex traits. Longitudinal studies further leverage epigenetic profiling to characterize dynamic changes in DNA methylation over time, helping researchers investigate how aging, environmental exposures, and disease progression may influence the epigenome. Together, NGS and microarray technologies offer complementary approaches to epigenomic research and integrate with Illumina’s bioinformatics ecosystem to enable scalable, high-quality epigenetic data generation and analysis.
NGS-based methods can enable comprehensive biological discovery, provide genome-wide methylation information, and reveal regional and allele-specific patterns. These sequencing-based methods also have the advantage of accommodating different sample types and low inputs.
Illumina’s 5-base solution is an NGS analysis workflow enabling whole-genome sequencing and whole-methylome sequencing for studies examining how cancer and other diseases develop and evolve. It identifies methylated cytosines (one of the four DNA bases, along with adenine, guanine and thymine), while simultaneously calling DNA variants—with all this data coming from a single sample. An enzyme converts methylated cytosines (5mC) into thymine, without affecting unmethylated cytosines. As a result, this technique can read all 5 bases—the As, Gs, Cs, Ts, and 5mCs—in a person’s genome.
The 5-base solution simultaneously provides genomic and epigenomic data to identify genetic variants, as well as how they are controlled. Layering genetic and epigenetic information will enhance discovery power across broad research applications, including cancer and rare disease. The novel approach can generate new and deeper biological insights, compared to genomic studies alone.
Another common NGS epigenetic technique is ChIP-seq, which helps determine how proteins interact with DNA to regulate gene expression. ChIP-Seq ChIP-seq uses an antibody to pull down DNA fragments bound by a specific protein, followed by NGS to identify and map the protein’s binding sites across the genome. This unbiased approach provides comprehensive information about histone modifications, gene regulatory networks, and other mechanisms to reveal their potential relationships to disease.
Microarray technology also remains a powerful and popular tool for DNA methylation research. Illumina Infinium Methylation arrays are known for their affordability and scalability, which supports profiling methylation in large cohort studies, such as the Million Veterans Program and UK Biobank. Methylation arrays are also regarded for delivering highly reproducible methylation data at individual methylation sites, and have supported the development of methylation classifiers for translational research, such as CNS tumor classifiers, rare disorder classifiers, and epigenetic aging clocks.
How researchers use epigenomics
The 5-base genome has the potential to uncover novel genetic and epigenetic markers of rare disease, providing insights into previously undiagnosed conditions. Methylation analysis complements whole-genome sequencing and whole-exome sequencing to accelerate discoveries in genetic disease research. In addition to rare disease, researchers have identified episignatures for over 150 neurodevelopmental disorders. The implications of DNA methylation also extend to neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. These conditions are characterized by distinct methylation patterns that shape gene expression.
Researchers at Pomeranian Medical University in Szczecin, Poland, are using 5-base to understand tumor classification through combined genome and epigenome profiling. The ability to generate both kinds of information could help researchers ask questions that were previously examined separately. A single dataset may contain information about small variants, structural changes, copy-number alterations, methylation patterns, and the interaction between those signals.
Because epigenetic tags are so sensitive to environmental changes, they provide an excellent barometer for health, disease, and toxic exposures. Studies can detect whether a person has been in contact with lead, cadmium, arsenic, mercury, and other toxins.
The future of epigenomics in precision medicine
Epigenomics is undoubtedly a key to true personalized medicine. Because these studies reveal changes in the behavior of an individual’s DNA—while their DNA sequences remain completely unchanged—it can help determine why cancer patients, for example, can exhibit similar genomic variations but have quite different therapeutic outcomes. The mechanisms that govern gene expression can play a powerful role.
In addition, as noted above, epigenetic techniques could dramatically advance early detection technologies. The ultimate payoff would be routine blood tests, like those used to assess cardiovascular risk, which could determine a patient’s chances of developing cancer.
But the benefits could go far beyond oncology. Epigenomics can identify biomarkers for many conditions, track disease progression and treatment effectiveness, and reveal new details about early development. In many ways, the epigenome is the genome’s operating system and fully understanding it will bring health benefits to millions.
