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  • All.sup.2: A tool for selec...
    Sarangi, Vivekananda; Jang, Yeongjun; Suvakov, Milovan; Bae, Taejeong; Fasching, Liana; Sekar, Shobana; Tomasini, Livia; Mariani, Jessica; Vaccarino, Flora M; Abyzov, Alexej

    PLoS computational biology, 04/2022, Volume: 18, Issue: 4
    Journal Article

    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, All.sup.2, 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 All.sup.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.