Bin Liu

Bin Liu, Jin Wang, Kaiwei Sun et al.

The discovery of drug-target interactions (DTIs) is a pivotal process in pharmaceutical development. Computational approaches are a promising and efficient alternative to tedious and costly wet-lab experiments for predicting novel DTIs from numerous candidates. Recently, with the availability of abundant heterogeneous biological information from diverse data sources, computational methods have been able to leverage multiple drug and target similarities to boost the performance of DTI prediction. Similarity integration is an effective and flexible strategy to extract crucial information across complementary similarity views, providing a compressed input for any similarity-based DTI prediction model. However, existing similarity integration methods filter and fuse similarities from a global perspective, neglecting the utility of similarity views for each drug and target. In this study, we propose a Fine-Grained Selective similarity integration approach, called FGS, which employs a local interaction consistency-based weight matrix to capture and exploit the importance of similarities at a finer granularity in both similarity selection and combination steps. We evaluate FGS on five DTI prediction datasets under various prediction settings. Experimental results show that our method not only outperforms similarity integration competitors with comparable computational costs, but also achieves better prediction performance than state-of-the-art DTI prediction approaches by collaborating with conventional base models. Furthermore, case studies on the analysis of similarity weights and on the verification of novel predictions confirm the practical ability of FGS.

Ao Zhou, Bin Liu, Jin Wang et al.

Class imbalance significantly impacts the performance of multi-label classifiers. Oversampling is one of the most popular approaches, as it augments instances associated with less frequent labels to balance the class distribution. Existing oversampling methods generate feature vectors of synthetic samples through replication or linear interpolation and assign labels through neighborhood information. Linear interpolation typically generates new samples between existing data points, which may result in insufficient diversity of synthesized samples and further lead to the overfitting issue. Deep learning-based methods, such as AutoEncoders, have been proposed to generate more diverse and complex synthetic samples, achieving excellent performance on imbalanced binary or multi-class datasets. In this study, we introduce AEMLO, an AutoEncoder-guided Oversampling technique specifically designed for tackling imbalanced multi-label data. AEMLO is built upon two fundamental components. The first is an encoder-decoder architecture that enables the model to encode input data into a low-dimensional feature space, learn its latent representations, and then reconstruct it back to its original dimension, thus applying to the generation of new data. The second is an objective function tailored to optimize the sampling task for multi-label scenarios. We show that AEMLO outperforms the existing state-of-the-art methods with extensive empirical studies.

Bin Liu, Dimitrios Papadopoulos, Fragkiskos D. Malliaros et al.

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.

Bin Liu, Grigorios Tsoumakas

In drug discovery, identifying drug-target interactions (DTIs) via experimental approaches is a tedious and expensive procedure. Computational methods efficiently predict DTIs and recommend a small part of potential interacting pairs for further experimental confirmation, accelerating the drug discovery process. Although it has been shown that fusing heterogeneous drug and target similarities can improve the prediction ability, the existing similarity combination methods ignore the interaction consistency for neighbour entities which is more crucial for the DTI prediction model. Furthermore, area under the precision-recall curve (AUPR) that emphasizes the accuracy of top-ranked pairs and area under the receiver operating characteristic curve (AUC) that heavily punishes the existence of low ranked interacting pairs are two widely used evaluation metrics in DTI prediction. However, the two metrics are seldom considered as losses within existing DTI prediction methods. This paper first proposes two matrix factorization (MF) methods that optimize AUPR and AUC using convex surrogate losses respectively, and then develops an ensemble MF approach takes advantage of the two area under the curve metrics by combining the two single metric based MF models. Both three proposed approaches incorporate a novel local interaction consistency aware similarity interaction method to generate fused drug and target similarities that preserve vital information from the more reliable view. Experimental results over five datasets under different prediction settings show that the proposed methods outperform various competitors in terms of the metric(s) they optimize. In addition, the validation on the top ranked novel predictions confirms the ability of our methods to discover potential new DTIs.

Bin Liu, Konstantinos Pliakos, Celine Vens et al.

Predicting drug-target interactions (DTI) via reliable computational methods is an effective and efficient way to mitigate the enormous costs and time of the drug discovery process. Structure-based drug similarities and sequence-based target protein similarities are the commonly used information for DTI prediction. Among numerous computational methods, neighborhood-based chemogenomic approaches that leverage drug and target similarities to perform predictions directly are simple but promising ones. However, existing similarity-based methods need to be re-trained to predict interactions for any new drugs or targets and cannot directly perform predictions for both new drugs, new targets, and new drug-target pairs. Furthermore, a large amount of missing (undetected) interactions in current DTI datasets hinders most DTI prediction methods. To address these issues, we propose a new method denoted as Weighted k-Nearest Neighbor with Interaction Recovery (WkNNIR). Not only can WkNNIR estimate interactions of any new drugs and/or new targets without any need of re-training, but it can also recover missing interactions (false negatives). In addition, WkNNIR exploits local imbalance to promote the influence of more reliable similarities on the interaction recovery and prediction processes. We also propose a series of ensemble methods that employ diverse sampling strategies and could be coupled with WkNNIR as well as any other DTI prediction method to improve performance. Experimental results over five benchmark datasets demonstrate the effectiveness of our approaches in predicting drug-target interactions. Lastly, we confirm the practical prediction ability of proposed methods to discover reliable interactions that were not reported in the original benchmark datasets.