All2: A tool for selecting mosaic mutations from comprehensive multi-cell comparisons

Accurate discovery of somatic mutations in a cell is a challenge that partially lays in immaturity of dedicated analytical approaches. Approaches comparing 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, All 2, which enables accurate filtering of mutations in a cell from exhaustive comparison of cells’ genomes to each other without data for bulk(s). Based on all pair-wise comparisons, every variant call (point mutation, indel, and structural variant) is classified as either a germline variant, mosaic mutation, or false positive. As All 2 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. All 2 is freely available at https://github.com/abyzovlab/All2 .