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

PLoS Comput Biol. 2022 Apr 20;18(4):e1009487. doi: 10.1371/journal.pcbi.1009487. eCollection 2022 Apr.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exome Sequencing
  • Exome*
  • High-Throughput Nucleotide Sequencing
  • INDEL Mutation / genetics
  • Mutation / genetics
  • Software*