SubcloneSeeker method overview. (A) Data preparation: genomic variation data (SNVs, CNVs, and so on) are converted into the corresponding cell prevalence (CP) values, and clustered into distinct groups. (B) Structure enumeration: based on the identified CP clusters, all possible subclone structures, represented as branching tree structures where one subclone is derived from its ‘predecessor’ by the addition of a mutation (or cluster of mutations), are visited. During the visit, each subclone on the tree structure is assigned a subclone frequency (SF) value so that the implied total CP values for mutations are in agreement with the input CP values. Those structures with negative SF values are removed from the solution set. (C) Solution trimming: the aim of this procedure is to merge the subclone structures from the relapse tumor (orange circles) those from the primary tumor (blue circles) from the same patient. Left panel: example showing a compatible pair of relapse/primary structures. Right panel: example showing a pair of incompatible relapse / primary subclone structures. A subclone in the relapse, R2, cannot be positioned anywhere within the primary subclone structure because it contains mutations found in separate primary subclones (P1 and P3.), and therefore cannot be derived from either one or the other.