One study introduced a likelihood-based method to detect shifts in trait-dependent evolution.60 More recently, the package SDevo linked tumor cell birth rates in a birth-death model to discrete states, specifically the position of cancer cells along the edges of a tumor.61 TyCHE differs from SDevo’s approach by allowing clock rates (rather than growth rates) to vary by cell type, introducing the EO approximation, and utilizing a simpler CTMC model. The gene discussed is CLOCK; the disease is cancer.