Quantifying circulating tumour DNA from liquid biopsies and application to lymphoma

Diffuse large B-cell lymphoma is an aggressive and heterogeneous type of non-Hodgkin lymphoma. Circulating tumour DNA (ctDNA) is composed of highly fragmented tumour- derived cell-free DNA (cfDNA) and can be extracted from a patient's bloodstream. This "liquid biopsy" contains tumour-specific genetic alterations inclusive of simple somatic mutations and copy number variations (CNVs). Quantifying ctDNA is challenging, as existing tools are inconsistent in determining the fraction of ctDNA in a plasma sample (known as the purity) and have variable sensitivity at low levels. Leveraging CAPP-Seq and low-pass WGS (lpWGS), I developed a bioinformatic program called PurEctDNA that estimates cfDNA purity levels with high accuracy across a broad range (5-100%). With this, I modified the CNV caller, WisecondorX, to infer purity and produce improved copy number profiles from lpWGS data. Utilizing these new methods could enable more accurate and sensitive detection of ctDNA from lymphoma patients thereby improving our ability to monitor disease progression non-invasively.