부산대학교 도서관

Accurate discovery of somatic mutations in a cell is a challenge that partially lays in immaturity of dedicated analytical approaches. Approaches comparing a cell's genome to a control bulk sample miss common mutations, while approaches to find such mutations from bulk suffer from low sensitivity. We developed a tool, All2, which enables accurate filtering of mutations in a cell without the need for data from bulk(s). It is based on pair-wise comparisons of all cells to each other where every call for base pair substitution and indel is classified as either a germline variant, mosaic mutation, or false positive. As All2 allows for considering dropped-out regions, it is applicable to whole genome and exome analysis of cloned and amplified cells. By applying the approach to a variety of available data, we showed that its application reduces false positives, enables sensitive discovery of high frequency mutations, and is indispensable for conducting high resolution cell lineage tracing. Author summary: DNA make up in cells of a human is slightly different from one another because of cell specific mutations called mosaic mutations. Mosaic mutations can be introduced during early development in a fetus, during normal cell division throughout life or during an aggressive onset of cell division such as cancer. Thus, the extent of accumulation, time of acquiring and specific location of mosaic mutations in the genome are vital for the understanding of the biology of normal development as well as diseases that are caused by it. The ultimate way of discovering and analyzing mosaic mutations is by studying the genome of single cells. Our method, All2, uses a novel approach to compare the genome of single cells to one another to accurately recognize true mosaic mutations from natural variations and from noise by implementing a unique scoring method. We have shown that our method performs better than discovery of mutations from a bulk or from comparing cells to a bulk. We have applied the method to high resolution cell lineage tracing and demonstrated it superb performance for reconstructing individualized cell ancestry trees starting from the zygote. [ABSTRACT FROM AUTHOR]