Eggle, M.; Mayakonda, A.; Bartenhagen, C.; Hofer, T.; Westermann, F.; Korber, V.

Computational tools for phylogenetic inference of early tumor evolution in real time are currently lacking. We present LACHESIS, a standardized R package and Shiny app that times early and most recent common ancestors of individual tumors from whole-genome sequencing data. LACHESIS automates mutational signature-aware molecular clock modeling for trajectory reconstruction and evolution-based risk stratification. We validate its utility for childhood and adult malignancies, providing a broadly applicable pan-cancer workflow.