Development of a system to simultaneously detect mutations and epigenetic marks

DNA是细胞的信息存储系统。它由四个组成单元（A、C、G和T）组成一条长链。许多疾病都起源于DNA序列的改变，最明显的是癌症。能够读取DNA已经彻底改变了生物医学研究，并带来了诊断疾病的新方法。我们现在知道，还有一些额外的“标点符号”，以C的化学修饰的形式，影响着DNA指令的执行方式。这些所谓的“表观遗传”标记不是遗传的，但它们深刻地影响着细胞的行为，对了解各种疾病都很重要。现有的读取这些表观遗传标记的方法比标准的DNA测序更昂贵，更困难。因此，DNA测序比表观遗传测序有更多的数据和更多的应用。在这个项目中，我们建议开发一种同时读取遗传和表观遗传信息的方法，与标准DNA测序相比，这种方法几乎没有额外的成本。为了做到这一点，我们正在利用我们最近开发的一种新的化学方法来测量表观遗传标记。我们将仔细生成测试数据，这些数据将用于训练机器学习算法，以优化测序方法的准确性，并为该技术建立最佳的实验参数。由此产生的方法将使常规查询患者的遗传背景成为可能，同时测量他们的表观遗传状态。这将导致对表观遗传学在疾病中的作用有更广泛的了解。

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.