With increases in the quantity and quality of healthcare related data, data mining tools have the potential to improve people’s standard of living through personalized and pre- dictive medicine. In this thesis we improve the state-of-the-art in data mining for several problems in the healthcare domain. In problems such as drug-drug interaction prediction and Alzheimer’s Disease (AD) biomarkers discovery and prioritization, current methods either require tedious feature engineering or have unsatisfactory performance. New effective computational tools are needed that can tackle these complex problems. In this dissertation, we develop new algorithms for two healthcare problems: high-order drug-drug interaction prediction and amyloid imaging biomarker prioritization in Alzheimer’s Disease. Drug-drug interactions (DDIs) and their associated adverse drug reactions (ADRs) represent a significant detriment to the public h ealth. Existing research on DDIs primarily focuses on pairwise DDI detection and prediction. Effective computational methods for high-order DDI prediction are desired. In this dissertation, I present a deep learning based model D3I for cardinality-invariant and order-invariant high-order DDI prediction. The proposed models achieve 0.740 F1 value and 0.847 AUC value on high-order DDI prediction, and outperform classical methods on order-2 DDI prediction. These results demonstrate the strong potential of D 3 I and deep learning based models in tackling the prediction problems of high-order DDIs and their induced ADRs. The second problem I consider in this thesis is amyloid imaging biomarkers discovery, for which I propose an innovative machine learning paradigm enabling precision medicine in this domain. The paradigm tailors the imaging biomarker discovery process to individual characteristics of a given patient. I implement this paradigm using a newly developed learning-to-rank method PLTR. The PLTR model seamlessly integrates two objectives for joint optimization: pushing up relevant biomarkers and ranking among relevant biomarkers. The empirical study of PLTR conducted on the ADNI data yields promising results to identify and prioritize individual-specific amyloid imaging biomarkers based on the individual’s structural MRI data. The resulting top ranked imaging biomarkers have the potential to aid personalized diagnosis and disease subtyping.