Development of a system to simultaneously detect mutations and epigenetic marks

DNA is the information storage system of the cell. It consists of four building blocks (A, C, G & T) that form a long chain. Many diseases have their origin in changes to the DNA sequence, most notably cancer. Being able to read DNA has revolutionised biomedical research and led to new ways to diagnose diseases.

We now know that there are additional "punctuation marks", in the form of chemical modifications on C's, which affect how the instructions in the DNA are executed. These so-called "epigenetic" marks are not inherited, but they profoundly influence the behaviour of cells, and are important to understand a wide range of diseases.

The existing methods to read these epigenetic marks are more expensive and more difficult to perform than standard DNA sequencing. As a result, there is a lot more data from, and more applications of, DNA sequencing than epigenetic sequencing.

In this project, we are proposing to develop a method to read genetic and epigenetic information at the same time, and at little to no extra cost compared to standard DNA sequencing. To do so, we are making use of a new chemical method for measuring epigenetic marks that we developed recently. We will carefully generate test data which will be used to train machine-learning algorithms to optimise the accuracy of the sequencing method, and to establish the best possible experimental parameters for this technique.

The resulting method will make it possible to routinely query a patient's genetic background, while simultaneously measuring their epigenetic state. This will lead to a much broader understanding of the role of epigenetics in disease.