Detecting the tissue of origin of circulating cell free DNA

Summary The aim of this project is to analyse sequence data on circulating cell free DNA to identify methylation patterns which indicate the tissue of origin.

Project Details

Cell-free DNA (cfDNA) originates from dying cells in the body, and hence has emerged as a potential non-invasive biomarker in the diagnosis and prognosis of various acute and chronic disorders, including cancer. It is present in various body fluids, including plasma, urine and saliva, which make it an attractive option for biomarker discovery. However, identifying the tissue of origin of cell free DNA remains challenging.

In this project the student will work on approaches for using methylation patterns to identify cell free DNA originating from heart tissue. We have collected cfDNA samples following acute-injury in pre-clinical model of heart failure in Ovis aires (Sheep). Samples were collected at different time points; baseline (prior to injury), 1hr, 4hr, 24hr, 1wk, 2wk, 4wk and 8wks post injuray. We noticed a significant increase in total cfDNA levels at 1hr and 4hr following acute injury. We have also generated whole genome bisulfite sequence data of Ovis aries heart tissue (left and right ventricles) from 3 biological replicates to characterise cardiac tissue-specific methylation patterns. We are currently sequencing cfDNA samples at baseline and at 1 hour following acute injury. This project will seek to match methylation patterns observed in whole-genome cfDNA with those specific to heart tissue methylation patterns.