A probabilistic approach for collective similarity-based drug-drug interaction prediction.

MOTIVATION: As concurrent use of multiple medications becomes ubiquitous among patients, it is crucial to characterize both adverse and synergistic interactions between drugs. Statistical methods for prediction of putative drug-drug interactions (DDIs) can guide in vitro testing and cut down significant cost and effort. With the abundance of experimental data characterizing drugs and their associated targets, such methods must effectively fuse multiple sources of information and perform inference over the network of drugs. RESULTS: We propose a probabilistic approach for jointly inferring unknown DDIs from a network of multiple drug-based similarities and known interactions. We use the highly scalable and easily extensible probabilistic programming framework Probabilistic Soft Logic We compare against two methods including a state-of-the-art DDI prediction system across three experiments and show best performing improvements of more than 50% in AUPR over both baselines. We find five novel interactions validated by external sources among the top-ranked predictions of our model. AVAILABILITY AND IMPLEMENTATION: Final versions of all datasets and implementations will be made publicly available. CONTACT: dsridhar@ucsc.edu.

Bias and Stability of Single Variable Classifiers for Feature Ranking and Selection.

Feature rankings are often used for supervised dimension reduction especially when discriminating power of each feature is of interest, dimensionality of dataset is extremely high, or computational power is limited to perform more complicated methods. In practice, it is recommended to start dimension reduction via simple methods such as feature rankings before applying more complex approaches. Single Variable Classifier (SVC) ranking is a feature ranking based on the predictive performance of a classifier built using only a single feature. While benefiting from capabilities of classifiers, this ranking method is not as computationally intensive as wrappers. In this paper, we report the results of an extensive study on the bias and stability of such feature ranking method. We study whether the classifiers influence the SVC rankings or the discriminative power of features themselves has a dominant impact on the final rankings. We show the common intuition of using the same classifier for feature ranking and final classification does not always result in the best prediction performance. We then study if heterogeneous classifiers ensemble approaches provide more unbiased rankings and if they improve final classification performance. Furthermore, we calculate an empirical prediction performance loss for using the same classifier in SVC feature ranking and final classification from the optimal choices.

Network-Based Drug-Target Interaction Prediction with Probabilistic Soft Logic.

Drug-target interaction studies are important because they can predict drugs' unexpected therapeutic or adverse side effects. In silico predictions of potential interactions are valuable and can focus effort on in vitro experiments. We propose a prediction framework that represents the problem using a bipartite graph of drug-target interactions augmented with drug-drug and target-target similarity measures and makes predictions using probabilistic soft logic (PSL). Using probabilistic rules in PSL, we predict interactions with models based on triad and tetrad structures. We apply (blocking) techniques that make link prediction in PSL more efficient for drug-target interaction prediction. We then perform extensive experimental studies to highlight different aspects of the model and the domain, first comparing the models with different structures and then measuring the effect of the proposed blocking on the prediction performance and efficiency. We demonstrate the importance of rule weight learning in the proposed PSL model and then show that PSL can effectively make use of a variety of similarity measures. We perform an experiment to validate the importance of collective inference and using multiple similarity measures for accurate predictions in contrast to non-collective and single similarity assumptions. Finally, we illustrate that our PSL model achieves state-of-the-art performance with simple, interpretable rules and evaluate our novel predictions using online data sets.

Confident Surgical Decision Making in Temporal Lobe Epilepsy by Heterogeneous Classifier Ensembles.

In medical domains with low tolerance for invalid predictions, classification confidence is highly important and traditional performance measures such as overall accuracy cannot provide adequate insight into classifications reliability. In this paper, a confident-prediction rate (CPR) which measures the upper limit of confident predictions has been proposed based on receiver operating characteristic (ROC) curves. It has been shown that heterogeneous ensemble of classifiers improves this measure. This ensemble approach has been applied to lateralization of focal epileptogenicity in temporal lobe epilepsy (TLE) and prediction of surgical outcomes. A goal of this study is to reduce extraoperative electrocorticography (eECoG) requirement which is the practice of using electrodes placed directly on the exposed surface of the brain. We have shown that such goal is achievable with application of data mining techniques. Furthermore, all TLE surgical operations do not result in complete relief from seizures and it is not always possible for human experts to identify such unsuccessful cases prior to surgery. This study demonstrates the capability of data mining techniques in prediction of undesirable outcome for a portion of such cases.