The discovery of drug-target interactions (DTIs) is a very promising area of research with great potential. The accurate identification of reliable interactions among drugs and proteins via computational methods, which typically leverage heterogeneous information retrieved from diverse data sources, can boost the development of effective pharmaceuticals. Although random walk and matrix factorization techniques are widely used in DTI prediction, they have several limitations. Random walk-based embedding generation is usually conducted in an unsupervised manner, while the linear similarity combination in matrix factorization distorts individual insights offered by different views. To tackle these issues, we take a multi-layered network approach to handle diverse drug and target similarities, and propose a novel optimization framework, called Multiple similarity DeepWalk-based Matrix Factorization (MDMF), for DTI prediction. The framework unifies embedding generation and interaction prediction, learning vector representations of drugs and targets that not only retain higher-order proximity across all hyper-layers and layer-specific local invariance, but also approximate the interactions with their inner product. Furthermore, we develop an ensemble method (MDMF2A) that integrates two instantiations of the MDMF model, optimizing the area under the precision-recall curve (AUPR) and the area under the receiver operating characteristic curve (AUC) respectively. The empirical study on real-world DTI datasets shows that our method achieves statistically significant improvement over current state-of-the-art approaches in four different settings. Moreover, the validation of highly ranked non-interacting pairs also demonstrates the potential of MDMF2A to discover novel DTIs.

Machine Learning (ML) is widely used for predictive tasks in a number of critical applications. Recently, collaborative or federated learning is a new paradigm that enables multiple parties to jointly learn ML models on their combined datasets. Yet, in most application domains, such as healthcare and security analytics, privacy risks limit entities to individually learning local models over the sensitive datasets they own. In this work, we present the first formal study for privacy-preserving collaborative hierarchical clustering, overall featuring scalable cryptographic protocols that allow two parties to privately compute joint clusters on their combined sensitive datasets. First, we provide a formal definition that balances accuracy and privacy, and we present a provably secure protocol along with an optimized version for single linkage clustering. Second, we explore the integration of our protocol with existing approximation algorithms for hierarchical clustering, resulting in a protocol that can efficiently scale to very large datasets. Finally, we provide a prototype implementation and experimentally evaluate the feasibility and efficiency of our approach on synthetic and real datasets, with encouraging results. For example, for a dataset of one million records and 10 dimensions, our optimized privacy-preserving approximation protocol requires 35 seconds for end-to-end execution, just 896KB of communication, and achieves 97.09% accuracy.