Abstract
To enable modularization for network-based prediction, we conducted a review of known methods conducting the various subtasks corresponding to the creation of a drug–target prediction framework and associated benchmarking to determine the highest-performing approaches. Accordingly, our contributions are as follows: (i) from a network perspective, we benchmarked the association-mining performance of 32 distinct subnetwork permutations, arranging based on a comprehensive heterogeneous biomedical network derived from 12 repositories; (ii) from a methodological perspective, we identified the best prediction strategy based on a review of combinations of the components with off-the-shelf classification, inference methods and graph embedding methods. Our benchmarking strategy consisted of two series of experiments, totaling six distinct tasks from the two perspectives, to determine the best prediction. We demonstrated that the proposed method outperformed the existing network-based methods as well as how combinatorial networks and methodologies can influence the prediction. In addition, we conducted disease-specific prediction tasks for 20 distinct diseases and showed the reliability of the strategy in predicting 75 novel drug–target associations as shown by a validation utilizing DrugBank 5.1.0. In particular, we revealed a connection of the network topology with the biological explanations for predicting the diseases, ‘Asthma’ ‘Hypertension’, and ‘Dementia’. The results of our benchmarking produced knowledge on a network-based prediction framework with the modularization of the feature selection and association prediction, which can be easily adapted and extended to other feature sources or machine learning algorithms as well as a performed baseline to comprehensively evaluate the utility of incorporating varying data sources.
Target-Specific Prediction of Ligand Affinity with Structure-Based Interaction Fingerprints
