Methods for the Detection of Single Nucleotide Variants and Indels from Cell-Free DNA

Successful development and application of precision oncology approaches require robust elucidation of the genomic landscape of a patient's cancer and the ability to monitor therapy-induced genomic changes in the tumour in an inexpensive and minimally invasive manner. Thanks to recent advances in sequencing technologies, "liquid biopsy", the sampling of patient's bodily fluids such as blood, is considered as one of the most promising approaches to achieve this goal. In many cancer patients, especially those with advanced metastatic disease, deep sequencing of cell-free DNA (cfDNA) obtained from patient's blood yields a mixture of reads originating from the normal DNA and from multiple tumour subclones - called circulating tumour DNA (ctDNA). The ctDNA/cfDNA ratio and the proportion of ctDNA originating from specific tumour subclones depend on multiple factors, making comprehensive detection of mutations difficult, especially at early stages of cancer. We introduce SiNVICT, a computational method for analysis of cfDNA sequencing data.