Every cell in an organism carries the same DNA, but not every cell uses the same genes. Epigenomics studies the marks that decide which genes are switched on and which are switched off, without changing the sequence. These marks respond to the environment, age or disease, and in many cases they are reversible.
If the genome is the text, epigenetics are the marks that say which parts get read. A methylation mark on a gene, or a protein bound to its regulatory region, can be enough to switch it on or off.
That is why two samples with the same genome behave differently. Epigenomics explains why a gene's expression changes, not only what changes, and provides stable markers that can be measured in blood or tissue.
Each technique looks at a different layer of regulation. The one that answers the question is chosen, or several are combined.
Methylation marks are measured position by position, across the whole genome or in regulatory regions.
DNA fragments bound to a specific protein, such as a transcription factor or a modified histone, are captured to map their positions in the genome.
RNAs bound to an RNA-binding protein are isolated to find out which ones it controls and how they change between conditions.
Some examples of the questions epigenomics helps answer:
Protective genes switched off by methylation, or genes switched on when they should not be.
Stable marks measurable in blood or tissue, useful for diagnosis and prognosis.
How age, diet, smoking or the environment leave a mark on the epigenome.
Whether a drug, a compound or an ingredient changes epigenetic marks.
Where a regulator binds the genome and which genes it controls.
Histone marks that distinguish active, repressed or poised regions.
Which RNAs an RNA-binding protein controls and how they change between conditions.
Stress response, development and adaptation in non-human species.
Epigenomics makes the most sense alongside gene expression. Measuring both layers in the same samples turns a list of changes into a mechanism:
Each sample is reviewed before analysis, to know which questions it can answer.
Differentially methylated regions or protein binding sites across the genome.
Which genes and biological processes are affected by the changes found.
What the results mean and what the next steps are.
An epigenetic change on its own does not always have an effect. Measuring expression in the same samples shows which changes have real consequences, and it is the most solid way to present them in a publication.
Starting from the question and the available samples, the most suitable technique is chosen and a proposal is prepared.