RADIOHEAD: Radiogenomic analysis incorporating tumor heterogeneity in imaging through densities

Recent technological advancements have enabled detailed investigation of associations between the molecular architecture and tumor heterogeneity, through multi-source integration of radiological imaging and genomic (radiogenomic) data. In this paper, we integrate and harness radiogenomic data in patients with lower grade gliomas (LGG), a type of brain cancer, in order to develop a regression framework called RADIOHEAD (RADIOgenomic analysis incorporating tumor HEterogeneity in imAging through Densities) to identify radiogenomic associations. Imaging data is represented through voxel intensity probability density functions of tumor subregions obtained from multimodal magnetic resonance imaging, and genomic data through molecular signatures in the form of pathway enrichment scores corresponding to their gene expression profiles. Employing a Riemannian-geometric framework for principal component analysis on the set of probability densities functions, we map each probability density to a vector of principal component scores, which are then included as predictors in a Bayesian regression model with the pathway enrichment scores as the response. Variable selection compatible with the grouping structure amongst the predictors induced through the tumor sub-regions is carried out under a group spike-and-slab prior. A Bayesian false discovery rate mechanism is then used to infer significant associations based on the posterior distribution of the regression coefficients. Our analyses reveal several pathways relevant to LGG etiology (such as synaptic transmission, nerve impulse and neurotransmitter pathways), to have significant associations with the corresponding imaging-based predictors.