Abstract A liquid biopsy is a non-invasive alternative to surgical biopsies which enables doctors to discover a range of information about a tumor through non-solid biological tissue, primarily blood. cell-free DNA (cfDNA) in human blood has emerged as an ideal source of genetic information for cancer detection and monitoring. cfDNA fragments are released by dying cells into the blood stream, including circulating tumor DNA that are released by tumor cells. In principle, tumor cfDNA contains genetic and epigenetic alterations identical to the tumor cells they originate from. These molecular alterations include (but not limited to) single nucleotide variations (SNV), structural variations, copy number variations, and DNA methylation changes. Next generation sequencing has been extensively used in “liquid biopsy” for targeted or genome-wide profiling of cfDNA. Given the inherent nature of cfDNA as a mixture of DNA fragments released from all possible cells in the body, and given the demand of sensitivity and specificity in detecting the tiny fraction of the ctDNA, specific bioinformatics tools are needed. However, currently no user-friendly and comprehensive bioinformatics tools exist to facilitate information extraction from cfDNA sequencing data. Given the enormous potential of cfDNA- based liquid biopsy in personalized medicine, this is an urgent demand to match. This proposal aims to match this need. Specifically, we will develop R-workflows for the analysis of cfDNA genomic and epigenomic sequencing data. We will extensively document the software toolkit, and provide detailed online manual so that non-expert users can easily learn and use all its functionalities.

Project Narrative This project will create the first software toolkit for the analysis and interpretation of cfDNA sequencing data. The methods and software package will significantly facilitate the information extraction from cfDNA data, and push forward the field of cfDNA-based diagnostics and monitoring.