Single cell profiling of breast tumors and the residing immune cells leveraged by integration with multi-dimensional molecular data from thousands of tumors
Breast cancer is the most common type of cancer in Europe, responsible for the highest women cancer mortalities each year. Characterisation of breast tumours teased them apart to distinct subtypes and facilitated targeted treatments that improved survival rates significantly, yet some aggressive subtypes remain difficult to treat. New therapies that harness the patient own immune system to fight the tumour show remarkable success in several cancers but limited one in breast cancer. Single cell genomics is the cutting-edge method to profile tissues at the highest resolution. As a computational biologist experienced in this technique, I will use it to analyse breast tumours with their residing immune cells. I aim to dissect the dynamic processes that shape the clonal development of the tumour as it emerges from a healthy tissue, with an emphasis on the immune system response to the evolving tumour. Single cell genomics, being the main driving tool, will be leveraged by integration with vast data from thousands of deeply profiled tumour samples available in the Host lab. The project includes generation of a healthy breast single cell expression atlas; a computational method to infer somatic mutations clones from single cell genomics data; single cell profiling of breast tumours together with adjacent normal tissues; and lastly, integration of the results with data from the large tumours biobank that holds years of clinical history which may reveal new progression markers and improve risk stratification. This plan is unique by accounting for multiple aspects of the tumours, including normal to malignant transition, interplay of breast and immune cells, and tumour clonal dynamics. By tackling common cancer immune mechanisms, it may provide novel insights of relevance to all cancer types. Pursuing this grand project in a leading lab that covers all aspects of breast cancer research will increase my research versatility on my way to become an independent researcher.