Fig. 1

Tumor evolution and cell phylogeny. a Schematic representation of tumor evolution with time progressing downwards. Stars denote new mutations leading to subclone expansion. The quadrangles belong to minor extinct subclones with no traces in the present-day populations. The mutations founding these clones may not have induced a sufficient growth advantage to have surviving descendant cells or may have been lost by chance. The gray discs on the bottom denote single cells sequenced after tumor removal. The stars they contain indicate the mutations observed in the cell. b Binary genealogical tree of the sequenced cells. An empty disc represents a normal somatic cell, which is an outgroup for the tumor cells. c Binary mutation matrix representing the mutation status of the sequenced tumor cells. A zero entry denotes the absence of a mutation in the respective cell, while a one denotes its presence. d The perfect phylogeny represented as a mutation tree, the partial (temporal) order of the mutation events. Mutations are summarized in a single node when their order is unidentifiable from the sampled cells, as is the case here for the two top-most mutations with the matrix from (c). e Hierarchical subclone structure. Cells with identical mutation profiles cluster into subclones, which serve as taxa in this phylogenetic tree. f Mutation tree with single-cell samples attached. g Noisy mutation matrix with missing values. The red numbers indicate flipped mutation states with respect to the true mutation matrix in (c). For 0→ 1, a false positive, the mutation is called but not present in the cell. For 1→ 0, a false negative, the mutation is not called but present in the cell, most likely due to allelic dropout during the DNA amplification. The red dash indicates a missing value; it is unknown whether the site is mutated or in the normal state in this cell