Dual role of histone activation: 2 scores were developed based on de novo chromatin activation, one associated with progressive (S_PD) and the other with indolent disease (S_ID). The combined balance score (S_B), calculated as the ratio of the S_PD to S_ID score, effectively stratifies patients into groups with different time to first treatment. Blue and red circles indicate H3K27ac peaks associated with indolent and progressive disease, respectively. Intermed, intermediate.