Knowledge Graph Completion to Predict Polypharmacy Side Effects

The polypharmacy side effect prediction problem considers cases in which two drugs taken individually do not result in a particular side effect; however, when the two drugs are taken in combination, the side effect manifests. In this work, we demonstrate that multi-relational knowledge graph completion achieves state-of-the-art results on the polypharmacy side effect prediction problem. Empirical results show that our approach is particularly effective when the protein targets of the drugs are well-characterized. In contrast to prior work, our approach provides more interpretable predictions and hypotheses for wet lab validation.Comment: 13th International Conference on Data Integration in the Life Sciences (DILS2018

A review of multi-instance learning assumptions

Multi-instance (MI) learning is a variant of inductive machine learning, where each learning example contains a bag of instances instead of a single feature vector. The term commonly refers to the supervised setting, where each bag is associated with a label. This type of representation is a natural fit for a number of real-world learning scenarios, including drug activity prediction and image classification, hence many MI learning algorithms have been proposed. Any MI learning method must relate instances to bag-level class labels, but many types of relationships between instances and class labels are possible. Although all early work in MI learning assumes a specific MI concept class known to be appropriate for a drug activity prediction domain; this ‘standard MI assumption’ is not guaranteed to hold in other domains. Much of the recent work in MI learning has concentrated on a relaxed view of the MI problem, where the standard MI assumption is dropped, and alternative assumptions are considered instead. However, often it is not clearly stated what particular assumption is used and how it relates to other assumptions that have been proposed. In this paper, we aim to clarify the use of alternative MI assumptions by reviewing the work done in this area

A Comparison of Multi-instance Learning Algorithms

Motivated by various challenging real-world applications, such as drug activity prediction and image retrieval, multi-instance (MI) learning has attracted considerable interest in recent years. Compared with standard supervised learning, the MI learning task is more difficult as the label information of each training example is incomplete. Many MI algorithms have been proposed. Some of them are specifically designed for MI problems whereas others have been upgraded or adapted from standard single-instance learning algorithms. Most algorithms have been evaluated on only one or two benchmark datasets, and there is a lack of systematic comparisons of MI learning algorithms. This thesis presents a comprehensive study of MI learning algorithms that aims to compare their performance and find a suitable way to properly address different MI problems. First, it briefly reviews the history of research on MI learning. Then it discusses five general classes of MI approaches that cover a total of 16 MI algorithms. After that, it presents empirical results for these algorithms that were obtained from 15 datasets which involve five different real-world application domains. Finally, some conclusions are drawn from these results: (1) applying suitable standard single-instance learners to MI problems can often generate the best result on the datasets that were tested, (2) algorithms exploiting the standard asymmetric MI assumption do not show significant advantages over approaches using the so-called collective assumption, and (3) different MI approaches are suitable for different application domains, and no MI algorithm works best on all MI problems

Positive-Unlabeled Learning for inferring drug interactions based on heterogeneous attributes

BACKGROUND: Investigating and understanding drug-drug interactions (DDIs) is important in improving the effectiveness of clinical care. DDIs can occur when two or more drugs are administered together. Experimentally based DDI detection methods require a large cost and time. Hence, there is a great interest in developing efficient and useful computational methods for inferring potential DDIs. Standard binary classifiers require both positives and negatives for training. In a DDI context, drug pairs that are known to interact can serve as positives for predictive methods. But, the negatives or drug pairs that have been confirmed to have no interaction are scarce. To address this lack of negatives, we introduce a Positive-Unlabeled Learning method for inferring potential DDIs. RESULTS: The proposed method consists of three steps: i) application of Growing Self Organizing Maps to infer negatives from the unlabeled dataset; ii) using a pairwise similarity function to quantify the overlap between individual features of drugs and iii) using support vector machine classifier for inferring DDIs. We obtained 6036 DDIs from DrugBank database. Using the proposed approach, we inferred 589 drug pairs that are likely to not interact with each other; these drug pairs are used as representative data for the negative class in binary classification for DDI prediction. Moreover, we classify the predicted DDIs as Cytochrome P450 (CYP) enzyme-Dependent and CYP-Independent interactions invoking their locations on the Growing Self Organizing Map, due to the particular importance of these enzymes in clinically significant interaction effects. Further, we provide a case study on three predicted CYP-Dependent DDIs to evaluate the clinical relevance of this study. CONCLUSION: Our proposed approach showed an absolute improvement in F1-score of 14 and 38% in comparison to the method that randomly selects unlabeled data points as likely negatives, depending on the choice of similarity function. We inferred 5300 possible CYP-Dependent DDIs and 592 CYP-Independent DDIs with the highest posterior probabilities. Our discoveries can be used to improve clinical care as well as the research outcomes of drug development