Unsupervised domain adaptation for medical imaging segmentation with self-ensembling.

Recent advances in deep learning methods have redefined the state-of-the-art for many medical imaging applications, surpassing previous approaches and sometimes even competing with human judgment in several tasks. Those models, however, when trained to reduce the empirical risk on a single domain, fail to generalize when applied to other domains, a very common scenario in medical imaging due to the variability of images and anatomical structures, even across the same imaging modality. In this work, we extend the method of unsupervised domain adaptation using self-ensembling for the semantic segmentation task and explore multiple facets of the method on a small and realistic publicly-available magnetic resonance (MRI) dataset. Through an extensive evaluation, we show that self-ensembling can indeed improve the generalization of the models even when using a small amount of unlabeled data.

Machine learning and big data analytics in bipolar disorder: A position paper from the International Society for Bipolar Disorders Big Data Task Force.

OBJECTIVES: The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD. METHOD: A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD. RESULTS: The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data-driven phenotypes, as well as by predicting transition to the disorder in high-risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non-stationary distribution of the data, and lack of appropriate funding. CONCLUSION: Machine learning-based studies, including atheoretical data-driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse-relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings.

Reduction strategies for hierarchical multi-label classification in protein function prediction.

BACKGROUND: Hierarchical Multi-Label Classification is a classification task where the classes to be predicted are hierarchically organized. Each instance can be assigned to classes belonging to more than one path in the hierarchy. This scenario is typically found in protein function prediction, considering that each protein may perform many functions, which can be further specialized into sub-functions. We present a new hierarchical multi-label classification method based on multiple neural networks for the task of protein function prediction. A set of neural networks are incrementally training, each being responsible for the prediction of the classes belonging to a given level. RESULTS: The method proposed here is an extension of our previous work. Here we use the neural network output of a level to complement the feature vectors used as input to train the neural network in the next level. We experimentally compare this novel method with several other reduction strategies, showing that it obtains the best predictive performance. Empirical results also show that the proposed method achieves better or comparable predictive performance when compared with state-of-the-art methods for hierarchical multi-label classification in the context of protein function prediction. CONCLUSIONS: The experiments showed that using the output in one level as input to the next level contributed to better classification results. We believe the method was able to learn the relationships between the protein functions during training, and this information was useful for classification. We also identified in which functional classes our method performed better.

Automatic design of decision-tree algorithms with evolutionary algorithms.

This study reports the empirical analysis of a hyper-heuristic evolutionary algorithm that is capable of automatically designing top-down decision-tree induction algorithms. Top-down decision-tree algorithms are of great importance, considering their ability to provide an intuitive and accurate knowledge representation for classification problems. The automatic design of these algorithms seems timely, given the large literature accumulated over more than 40 years of research in the manual design of decision-tree induction algorithms. The proposed hyper-heuristic evolutionary algorithm, HEAD-DT, is extensively tested using 20 public UCI datasets and 10 microarray gene expression datasets. The algorithms automatically designed by HEAD-DT are compared with traditional decision-tree induction algorithms, such as C4.5 and CART. Experimental results show that HEAD-DT is capable of generating algorithms which are significantly more accurate than C4.5 and CART.

Automatic design of decision-tree induction algorithms tailored to flexible-receptor docking data.

BACKGROUND: This paper addresses the prediction of the free energy of binding of a drug candidate with enzyme InhA associated with Mycobacterium tuberculosis. This problem is found within rational drug design, where interactions between drug candidates and target proteins are verified through molecular docking simulations. In this application, it is important not only to correctly predict the free energy of binding, but also to provide a comprehensible model that could be validated by a domain specialist. Decision-tree induction algorithms have been successfully used in drug-design related applications, specially considering that decision trees are simple to understand, interpret, and validate. There are several decision-tree induction algorithms available for general-use, but each one has a bias that makes it more suitable for a particular data distribution. In this article, we propose and investigate the automatic design of decision-tree induction algorithms tailored to particular drug-enzyme binding data sets. We investigate the performance of our new method for evaluating binding conformations of different drug candidates to InhA, and we analyze our findings with respect to decision tree accuracy, comprehensibility, and biological relevance. RESULTS: The empirical analysis indicates that our method is capable of automatically generating decision-tree induction algorithms that significantly outperform the traditional C4.5 algorithm with respect to both accuracy and comprehensibility. In addition, we provide the biological interpretation of the rules generated by our approach, reinforcing the importance of comprehensible predictive models in this particular bioinformatics application. CONCLUSIONS: We conclude that automatically designing a decision-tree algorithm tailored to molecular docking data is a promising alternative for the prediction of the free energy from the binding of a drug candidate with a flexible-receptor.

Explainable Machine Learning for COVID-19 Pneumonia Classification With Texture-Based Features Extraction in Chest Radiography.

Both reverse transcription-PCR (RT-PCR) and chest X-rays are used for the diagnosis of the coronavirus disease-2019 (COVID-19). However, COVID-19 pneumonia does not have a defined set of radiological findings. Our work aims to investigate radiomic features and classification models to differentiate chest X-ray images of COVID-19-based pneumonia and other types of lung patterns. The goal is to provide grounds for understanding the distinctive COVID-19 radiographic texture features using supervised ensemble machine learning methods based on trees through the interpretable Shapley Additive Explanations (SHAP) approach. We use 2,611 COVID-19 chest X-ray images and 2,611 non-COVID-19 chest X-rays. After segmenting the lung in three zones and laterally, a histogram normalization is applied, and radiomic features are extracted. SHAP recursive feature elimination with cross-validation is used to select features. Hyperparameter optimization of XGBoost and Random Forest ensemble tree models is applied using random search. The best classification model was XGBoost, with an accuracy of 0.82 and a sensitivity of 0.82. The explainable model showed the importance of the middle left and superior right lung zones in classifying COVID-19 pneumonia from other lung patterns.

Clustering molecular dynamics trajectories for optimizing docking experiments.

Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.