Lymphocyte_Liver_WGS_H38

As we age, our cells accumulate mutations, termed "somatic mutations". Somatic mutations, which exist in mosaic form throughout the body, are a direct record of the evolution of our cells. Some of these mutations are subject to neutral evolution. The study of neutral mutations can reveal the cell lineages resulting from normal development and tissue maintenance, and help us understand key demographic parameter of somatic evolution, such as population size and migration. Other mutations are under selection, resulting in the expansion or contraction of lineages. These mutations can lead to disease, such as cancer; however, the extent of selection on somatic mutations in not understood. We aim to understand the somatic evolution of the primary cells of the adaptive immune system, lymphocytes. As we age, lymphocytes accumulate somatic mutations, which reveal the evolutionary history of lymphocytes, as well as providing information about the particular mutations and lineage structures that contribute to age-related immune disorder. In order to understand somatic evolution in lymphocytes in a disease context, we sequence lymphocytes from cirrhotic liver samples across multiple donors. We perform whole-genome sequencing of single-cell derived T and B cell colonies to identify somatic mutations, and perform targeted deep-sequencing of these mutations. The lineages of T and B cells, and the frequencies of these mutations reveals the neutral and non-neutral evolutionary processes underlying lymphocyte growth.