A novel integrative computational framework for breast cancer radiogenomic biomarker discovery.

In precise medicine, it is with great value to develop computational frameworks for identifying prognostic biomarkers which can capture both multi-genomic and phenotypic heterogeneity of breast cancer (BC). Radiogenomics is a field where medical images and genomic measurements are integrated and mined to solve challenging clinical problems. Previous radiogenomic studies suffered from data incompleteness, feature subjectivity and low interpretability. For example, the majority of the radiogenomic studies miss one or two of medical imaging data, genomic data, and clinical outcome data, which results in the data incomplete issue. Feature subjectivity issue comes from the extraction of imaging features with significant human involvement. Thus, there is an urgent need to address above-mentioned limitations so that fully automatic and transparent radiogenomic prognostic biomarkers could be identified for BC. We proposed a novel framework for BC prognostic radiogenomic biomarker identification. This framework involves an explainable DL model for image feature extraction, a Bayesian tensor factorization (BTF) processing for multi-genomic feature extraction, a leverage strategy to utilize unpaired imaging, genomic, and survival outcome data, and a mediation analysis to provide further interpretation for identified biomarkers. This work provided a new perspective for conducting a comprehensive radiogenomic study when only limited resources are given. Compared with baseline traditional radiogenomic biomarkers, the 23 biomarkers identified by the proposed framework performed better in indicating patients' survival outcome. And their interpretability is guaranteed by different levels of build-in and follow-up analyses.