49382Base Genomics: A novel method for single-step, ultra-sensitive, combined DNA methylation and mutation detection of cancer from liquid biopsies using WGSClosedCollaborative R&DISCFThe 100,000 Genome Project and other similar efforts have clearly demonstrated that many disease processes including cancer, are caused by acquired changes in the genetic material of tissue called DNA. There are many different types of DNA changes such as "DNA mutations" and "DNA methylation". However, none of the currently available sequencing methods reliably detects all of these DNA changes at any one time in the same experiment. The combined and simultaneous identification of acquired DNA mutations together with DNA methylation from the same tissue is therefore considered as the "holy grail" of cancer diagnostics and academic research. Existing methods to detect DNA methylation such as a method called "bisulfite sequencing (BS)" destroy most of the DNA. It means that these methods are not very sensitive, results remain often uncertain and the sequencing process is very expensive. Importantly, it also means that these methods require more DNA as starting material which is often difficult to obtain, especially from clinical tissue that comes from small cancer biopsies. This is a particular challenge for the analysis of so called "liquid biopsies" that are obtained from a simple blood draw and that contain small amounts of circulating tumour DNA. Liquid biopsies are a non-invasive method that might be used in future to diagnose cancer much earlier and also to monitor whether patients with cancer respond to therapy as -contrary to cancer tissue biopsies- liquid biopsies can be repeated easily many times. Base Genomics have developed a completely novel method called "TAPS" that simultaneously detects DNA mutations and DNA methylation, does not destroy DNA and that therefore allows sensitive detection of acquired DNA changes in a single sequencing experiments from low amounts of DNA. Compared to existing methods, TAPS also provides more precise results at lower sequencing costs. Here, we will make use of samples and WGS data from the Genomics England Cancer Pilot. In the first set of experiments, we specifically compare TAPS to existing methods using liquid biopsies from patients with early stage cancer to test whether TAPS is superior in detecting both DNA mutations and DNA methylation changes from liquid biopsies that are specific to cancer tissue. If this is the case, we will go on to test in a larger cohort, whether TAPS can correctly identify patients with cancer from liquid biopsies. Together, these experiments will demonstrate TAPS as a highly promising tool for academic research and clinical cancer diagnostics.