Figure 2
Overview of the TuMult algorithm. (a) Discretized copy number profiles of three tumors from the same patient (yellow, 'normal copy number'; green, 'loss'; red, 'gain'). The eight breakpoints identified in the samples (dashed lines) divide the chromosome into seven 'homogeneous segments', A to G, in which copy number is constant in any sample. The profiles can be represented as amplitude vectors (see Materials and methods), in which 'up' and 'down' breakpoints are distinguished by their position in the vector. A common breakpoint (gray shading) appears as a non-zero value at the same position in the amplitude matrix. The frequency Fk of each breakpoint is calculated from a reference data set of independent samples. (b) An identical breakpoint score (IBS), characterizing the similarity of two profiles in terms of chromosome breakpoints, is calculated for each pair of samples, and the pair displaying the highest level of similarity is selected. (c) The copy number profile of the common precursor of the two samples is reconstructed based on their common breakpoints, represented by dashed lines and black arrows. Edges are added between the common precursor (CP) and the two nodes, labeled with the aberrations defined by their specific breakpoints, represented by gray arrows. Note that a breakpoint may be both common and specific, if its amplitude is larger in one of the samples, like the 'down' breakpoint between segments A and B in this example. (d) Steps (b) and (c) are iterated until there is only one node left in the front. (e) A 'normal cell' node has been added above the common ancestor of all tumors.