Development of a system to simultaneously detect mutations and epigenetic marks

开发同时检测突变和表观遗传标记的系统

• 批准号: MR/T04490X/1
• 负责人: Philip Schuster-Boeckler
• 金额: $ 53.57万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT04490X%2F1
• 关键词: Development; system; simultaneously; detect; mutations

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.

DNA是细胞的信息存储系统。它由形成长链的四个构建块（A、C、G 和 T）组成。许多疾病的根源在于 DNA 序列的变化，尤其是癌症。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，还有额外的“标点符号”，以 C 上的化学修饰的形式存在，这会影响 DNA 中指令的执行方式。这些所谓的“表观遗传”标记不是遗传性的，但它们深刻地影响着细胞的行为，对于了解多种疾病非常重要。读取这些表观遗传标记的现有方法比标准 DNA 测序更昂贵且更难以执行。因此，与表观遗传测序相比，DNA 测序产生的数据更多，应用也更多。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，几乎不需要额外成本。为此，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，同时测量其表观遗传状态。这将使人们对表观遗传学在疾病中的作用有更广泛的了解。

项目成果

Cell-free DNA TAPS provides multimodal information for early cancer detection.

• DOI: 10.1126/sciadv.abh0534
• 发表时间: 2021-09-03
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Siejka-Zielińska P;Cheng J;Jackson F;Liu Y;Soonawalla Z;Reddy S;Silva M;Puta L;McCain MV;Culver EL;Bekkali N;Schuster-Böckler B;Palamara PF;Mann D;Reeves H;Barnes E;Sivakumar S;Song CX
• 通讯作者: Song CX

Platelets Sequester Extracellular DNA, Capturing Tumour-Derived and Free Fetal DNA

血小板隔离细胞外 DNA，捕获肿瘤源性 DNA 和游离胎儿 DNA

• DOI: 10.1182/blood-2023-182697
• 发表时间: 2023
• 期刊: Blood
• 影响因子: 20.3
• 作者: Murphy L