Fig. 1.

Model for clonal evolution and inference. (A) An example of the evolution of a tumor containing seven distinct clones. Passenger mutations (white) occurring before the first clonal expansion will be indistinguishable from mutations driving the growth of the founding clone (light blue). Each subsequent mutation (green, purple, dark blue, orange, red and tan) creates a new clone. (B) Three sequenced tumor samples. Some clones may no longer exist at the time of sequencing (orange). Samples 1 and 2 each contain a single clone (purple and blue respectively), whereas Sample 3 is a mixture of three clones (light blue, red and tan). (C) The frequency matrix F observed for the three sequenced samples indicated in part B. (D) The usage matrix U and clonal matrix B that generate F. Even though some clones existing at the current time may not be contained within a sequenced sample (green), their existence in the evolutionary history of the tumor may be recovered. (E) Tree of the inferred tumor clones. Solid black edges are the clonal tree T corresponding to the clonal matrix B. Gray dashed edges indicate internal vertices used in the mixing of some sample. The number next to each clone in each sample indicates the fraction of cells in the sample from that clone. (F) The ancestry graph for the observed data. The bold arcs indicate the spanning arborescence corresponding to T