Accelerating the Development and Validation of Liquid Biopsy Assays for Cancer

Liquid biopsies, such as blood plasma containing cell-free DNA, provide a non-invasive route to profile tumor genomes in precision medicine. Current research and clinical efforts have largely focused on detecting mutations in select cancer genes from circulating tumor DNA (ctDNA) found in cell-free DNA. However, solutions to characterize and integrate genome-wide alterations and epigenetic profiling can further improve the detection of ctDNA in cancer patients. We propose to develop novel computational approaches for high-sensitivity copy number and tissue-of-origin analysis from scalable low-pass whole genome sequencing of cell-free DNA. We will apply these approaches to study metastatic castration-resistant prostate cancer (mCRPC), a lethal disease with no curative treatment. Using the rich clinical annotations and serial blood samples collected during therapy, we will identify features and alterations in ctDNA that may be implicated in treatment resistance. These innovations will be critical to establishing an accurate clinical cfDNA diagnostic workflow and will accelerate the discovery of blood-based genomic biomarkers in cancer.