A NEW METHODOLOGY FOR IDENTIFYING INTERFACE RESIDUES INVOLVED IN BINDING PROTEIN COMPLEXES

Genome-sequencing projects with advanced technologies have rapidly increased the amount of protein sequences, and demands for identifying protein interaction sites are significantly increased due to its impact on understanding cellular process, biochemical events and drug design studies. However, the capacity of current wet laboratory techniques is not enough to handle the exponentially growing protein sequence data; therefore, sequence based predictive methods identifying protein interaction sites have drawn increasing interest. In this article, a new predictive model which can be valuable as a first approach for guiding experimental methods investigating protein-protein interactions and localizing the specific interface residues is proposed. The proposed method extracts a wide range of features from protein sequences. Random forests framework is newly redesigned to effectively utilize these features and the problems of imbalanced data classification commonly encountered in binding site predictions. The method is evaluated with 2,829 interface residues and 24,616 non-interface residues extracted from 99 polypeptide chains in the Protein Data Bank. The experimental results show that the proposed method performs significantly better than two other conventional predictive methods and can reliably predict residues involved in protein interaction sites. As blind tests, the proposed method predicts interaction sites and constructs three protein complexes: the DnaK molecular chaperone system, 1YUW and 1DKG, which provide new insight into the sequence-function relationship. Finally, the robustness of the proposed method is assessed by evaluating the performances obtained from four different ensemble methods

Use of ensemble based on GA for imbalance problem

In real-world applications, it has been observed that class imbalance (significant differences in class prior probabilities) may produce an important deterioration of the classifier performance, in particular with patterns belonging to the less represented classes. One method to tackle this problem consists to resample the original training set, either by over-sampling the minority class and/or under-sampling the majority class. In this paper, we propose two ensemble models (using a modular neural network and the nearest neighbor rule) trained on datasets under-sampled with genetic algorithms. Experiments with real datasets demonstrate the effectiveness of the methodology here propose

Machine Learning Approaches for Improving Prediction Performance of Structure-Activity Relationship Models

In silico bioactivity prediction studies are designed to complement in vivo and in vitro efforts to assess the activity and properties of small molecules. In silico methods such as Quantitative Structure-Activity/Property Relationship (QSAR) are used to correlate the structure of a molecule to its biological property in drug design and toxicological studies. In this body of work, I started with two in-depth reviews into the application of machine learning based approaches and feature reduction methods to QSAR, and then investigated solutions to three common challenges faced in machine learning based QSAR studies. First, to improve the prediction accuracy of learning from imbalanced data, Synthetic Minority Over-sampling Technique (SMOTE) and Edited Nearest Neighbor (ENN) algorithms combined with bagging as an ensemble strategy was evaluated. The Friedman’s aligned ranks test and the subsequent Bergmann-Hommel post hoc test showed that this method significantly outperformed other conventional methods. SMOTEENN with bagging became less effective when IR exceeded a certain threshold (e.g., \u3e40). The ability to separate the few active compounds from the vast amounts of inactive ones is of great importance in computational toxicology. Deep neural networks (DNN) and random forest (RF), representing deep and shallow learning algorithms, respectively, were chosen to carry out structure-activity relationship-based chemical toxicity prediction. Results suggest that DNN significantly outperformed RF (p \u3c 0.001, ANOVA) by 22-27% for four metrics (precision, recall, F-measure, and AUPRC) and by 11% for another (AUROC). Lastly, current features used for QSAR based machine learning are often very sparse and limited by the logic and mathematical processes used to compute them. Transformer embedding features (TEF) were developed as new continuous vector descriptors/features using the latent space embedding from a multi-head self-attention. The significance of TEF as new descriptors was evaluated by applying them to tasks such as predictive modeling, clustering, and similarity search. An accuracy of 84% on the Ames mutagenicity test indicates that these new features has a correlation to biological activity. Overall, the findings in this study can be applied to improve the performance of machine learning based Quantitative Structure-Activity/Property Relationship (QSAR) efforts for enhanced drug discovery and toxicology assessments

Evaluation methods and decision theory for classification of streaming data with temporal dependence

Predictive modeling on data streams plays an important role in modern data analysis, where data arrives continuously and needs to be mined in real time. In the stream setting the data distribution is often evolving over time, and models that update themselves during operation are becoming the state-of-the-art. This paper formalizes a learning and evaluation scheme of such predictive models. We theoretically analyze evaluation of classifiers on streaming data with temporal dependence. Our findings suggest that the commonly accepted data stream classification measures, such as classification accuracy and Kappa statistic, fail to diagnose cases of poor performance when temporal dependence is present, therefore they should not be used as sole performance indicators. Moreover, classification accuracy can be misleading if used as a proxy for evaluating change detectors with datasets that have temporal dependence. We formulate the decision theory for streaming data classification with temporal dependence and develop a new evaluation methodology for data stream classification that takes temporal dependence into account. We propose a combined measure for classification performance, that takes into account temporal dependence, and we recommend using it as the main performance measure in classification of streaming data