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Breakage-Fusion-Bridge (BFB) is a mechanism of genomic instabilitycharacterized by the joining and subsequent tearing apart of sister chromatids.When this process is repeated during multiple rounds of cell division, it leadsto patterns of copy number increases of chromosomal segments as well asfold-back inversions where duplicated segments are arranged head-to-head. Thesestructural variations can then drive tumorigenesis.  BFB can be observed in progress using cytogenetic techniques, but generallyBFB must be inferred from data like microarrays or sequencing collected afterBFB has ceased. Making correct inferences from this data is notstraightforward, particularly given the complexity of some cancer genomes andBFB's ability to generate a wide range of rearrangement patterns.  Here we present algorithms to aid the interpretation of evidence for BFB. Wefirst pose the BFB count vector problem: given a chromosome segmentation andsegment copy numbers, decide whether BFB can yield a chromosome with the givensegment counts. We present the first linear-time algorithm for the problem,improving a previous exponential-time algorithm. We then combine this algorithmwith fold-back inversions to develop tests for BFB. We show that, contingent onassumptions about cancer genome evolution, count vectors and fold-backinversions are sufficient evidence for detecting BFB. We apply the presentedtechniques to paired-end sequencing data from pancreatic tumors and confirm aprevious finding of BFB as well as identify a new chromosomal region likelyrearranged by BFB cycles, demonstrating the practicality of our approach.

Detecting Breakage Fusion Bridge cycles in tumor genomes -- an algorithmic approach