Bisulfite-free and base-resolution cell-free DNA epigenetic sequencing for cancer diagnostics

Project Overview

Bisulfite-free, base-resolution, and quantitative sequencing of cytosine modifications with TAPS ...

Cell-free DNA epigenetic sequencing with TAPS and CAPS for cancer detection.

Background

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the two major epigenetic modifications found in the mammalian genome and they played important roles in a broad range of biological processes from gene regulation to initiation and progression of many human diseases. Therefore, epigenetic modifications are valuable biomarkers for diagnostics. Circulating cell-free DNA (cfDNA) is the DNA found in our bloodstream, which provides a noninvasive window for disease diagnosis. Although there has been great interest in using cfDNA as liquid biopsies for cancer detection, it has been challenging to identify the tissue-of-origin of cfDNA and hence the location of the tumour. Detecting epigenetic information such as 5mC and 5hmC in cfDNA is attractive for early cancer detection because it is known to be tissue and cancer-specific. Despite both a strong need and a compelling hypothesis for using epigenetic information in cfDNA for noninvasive diagnostics, it is far less explored than genetic information because the current methods (bisulfite sequencing) for detecting DNA epigenetic modifications are not feasible for the low amounts of highly fragmented cfDNA.

Aims and Objectives

We combine various chemical biology and genome technologies to develop novel tools in epigenetics. Recently we developed novel bisulfite-free and base-resolution sequencing technologies for DNA methylation and hydroxymethylation (bioRxiv doi: https://doi.org/10.1101/307538, Figure 1). It could replace bisulfite sequencing as the new standard in DNA epigenetic analysis. We expect it to revolutionize DNA epigenetic analysis, and to have wide applications in academic research and clinical diagnostics, especially in sensitive low-input samples, such as circulating cell-free DNA and single-cell analysis. This project aims to apply this method to develop comprehensive, systematic, and unbiased sequencing of the circulating cell-free methylation and hydroxymethylation (Figure 2). It will be applied to cell-free DNA from various solid tumours, with a focus on extracting tissue and disease-specific information for early detection. 

Training Opportunities

Training opportunities include a wide range of basic and advanced molecular biology/biochemistry/chemical biology techniques, as well as next-generation sequencing techniques and bioinformatics data-analysis. Training will be provided in all of these areas.

Theme

Genetics & Genomics and Cancer Biology

Admissions

Project reference number: 831

Funding and admissions information

Supervisors

Name Department Institution Country Email
Dr Chunxiao Song Oxford Ludwig Institute Oxford University, NDM Research Building GBR chunxiao.song@ludwig.ox.ac.uk
Dr Benjamin Schuster-Böckler Oxford Ludwig Institute Oxford University, Old Road Campus Research Building GBR benjamin.schuster-boeckler@ludwig.ox.ac.uk

There are no publications listed for this DPhil project.