Random survival forest modeling and Cox proportional hazards regression analysis determined imaging habitats 2,7, and 10 to be both important (+ve variable importance) and significant (p-value < 0.05) for determining OS after adjustment for covariates of age, Karnofsky performance score, tumor volume, and IDH1 mutation status (P < 0.05, Supplementary Table 1). These three habitats were thus designated as “relevant” habitats. The process of acquiring these relevant habitats is described in Figure 2. They represent distinct tumor sub-regions of clinical relevance to outcome in GBM, after adjusting for clinical covariates. Their relevance, coupled with the availability of matched genomic data for these patients, enables us to study the molecular mechanisms (pathway activities) associated with the presence of these habitats in GBM.