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Risk stratification (characterization) of tumors from radiology images can be more accurate and faster with computer-aided diagnosis (CAD) tools. Tumor characterization through such tools can also enable non-invasive cancer staging, prognosis, and foster personalized treatment planning as a part of precision medicine. In this paper, we propose both supervised and unsupervised machine learning strategies to improve tumor characterization. Our first approach is based on supervised learning for which we demonstrate significant gains with deep learning algorithms, particularly by utilizing a 3D convolutional neural network and transfer learning. Motivated by the radiologists' interpretations of the scans, we then show how to incorporate task-dependent feature representations into a CAD system via a graph-regularized sparse multi-task learning framework. In the second approach, we explore an unsupervised …