Figure 1. The Evo-index and how it changes.

a | The evolutionary index (Evo-index) is composed of two factors corresponding to heterogeneity over space (diversity, D) and heterogeneity over time (change over time, Δ). By ‘change’, we mean both change in the genetic, epigenetic and phenotypic alterations present in the population and change in the frequencies of those alterations in the neoplastic cell population. What measures of D and Δ are best is an open question. In addition, how these factors should be stratified into two, three or more classes is also an open question. Here, for simplicity, we provide examples of the kinds of dynamics that could be categorized into a simple 2 × 2 classification. b | The genetic composition of a tumour may change either slowly (Δ1) or rapidly (Δ2) in a variety of ways. On the left, a tumour may have low diversity (D1) at time 0 because it is a new tumour or there has been a recent homogenizing clonal expansion. That tumour may be quiescent and so appear substantially the same at time 1 (D1Δ1), or it may accumulate clones, some of which expand, to generate a diverse tumour by time 1 (D2Δ2). Alternatively, a tumour may be diverse (D2) at time 0 because it is old or has a high mutation rate and is evolving neutrally. At time 1, that tumour may have been homogenized by a selective sweep (D1Δ2) or may continue on its current trajectory with gradual turnover of its clones (D2Δ1).