Nucleosomics analysis of cell-free DNA for patient stratification

Nucleosome positioning is a key process in gene regulation and may vary throughout cell differentiation stages and in response to healthy and disease-related processes. In this project I examined different methods of using nucleosome positioning reconstructed from cell-free DNA (cfDNA) as part of a method for patient diagnostics and stratification. These results contributed to the development of two novel methods: one involving stratification of patients based on condition-specific changes in nucleosome occupancy, and another one based on distances between nucleosomes. Using these two methods, I analysed nucleosome positioning reconstructed from cfDNA in healthy people and patients with breast cancer and small cell lung cancer (SCLC), as well as in paired normal/tumour breast tissues. In addition, I have analysed the effect of ageing on the nucleosome patterns reconstructed from cfDNA. Both methods successfully distinguish cancer from healthy, as well as different age groups. CfDNA diagnostic methods based on nucleosome positioning have a potential to bring significant improvements in the clinic.