BreakLoops: A New Feature for the Multi-Gene, Multi-Cancer Family History-Based Model, Fam3Pro

Abstract Previously, we presented PanelPRO, now known as Fam3PRO, an open-source R package for multi-gene, multi-cancer risk modeling with pedigree data. The initial release could not handle pedigrees that contained cyclic structures called loops, which occur when relatives mate. Here, we present a graph-based function called breakloops that can detect and break loops in any pedigree. The core algorithm identifies the optimal set of loop breakers when individuals in a loop have exactly one parental mating, and extends to handle cases where individuals have multiple parental matings. The algorithm transforms complex pedigrees by strategically creating clones of key individuals to disrupt cycles while minimizing computational complexity. Our extensive testing demonstrates that this new feature can handle a wide variety of pedigree structures. The breakloops function is available in Fam3Pro version 2.0.0. This advancement enables Fam3Pro to assess cancer risk in a wider range of family structures, enhancing its applicability in clinical settings.