Epigenomic profiling of circulating free floating DNA

The plasma contains free floating cell-free DNA (cfDNA). cfDNA could be released by cell apoptosis or/and necrosis from all cell types or be actively secreted by the cell. The interest in clinical utility of cfDNA as a non-invasive biomarker has grown rapidly in recent years. Non-Invasive Prenatal Testing (NIPT) is a cfDNA-based screening tool that analyzes cfDNA derived from the fetus in maternal plasma to detect fetal aneuploidies. The test, at first applied to high-risk patients, has been rapidly adopted by health care providers and it is now validated for 13, 18, 21 trisomies and fetal sex detection. In oncology, cfDNA analysis could be a useful tool for the early diagnosis, the detection of minimal residual disease, and the evaluation of treatment response/progression. We developed a method to map genome-wide chromosomal imbalances in the cfDNA. However, this approach does not determine the tissue of origin of the cfDNA. Understanding the genesis of cfDNA can be informative not only about the type of cancer, but also pinpoint potentially several diseases. Secondly, the power of detection of GipSeq is restricted to copy number alteration. In this thesis, we will develop the algorithmic and computational analysis pipelines to map the methylation in cfDNA and deconvolute the signals to the tissue of origin. This will ultimately increase the sensitivity and specificity of early cancer detection, will leverage presymptomatic detection of cancers and may identify the origin of non-cancer related cfDNA fraction.