Breast cancer is associated with the highest morbidity rates for cancer diagnoses in the world and has become a major public health issue. Early diagnosis can increase the chance of successful treatment and survival. However, it is a very challenging and time-consuming task that relies on the experience of pathologists. The automatic diagnosis of breast cancer by analyzing histopathological images plays a significant role for patients and their prognosis. However, traditional feature extraction methods can only extract some low-level features of images, and prior knowledge is necessary to select useful features, which can be greatly affected by humans. Deep learning techniques can extract high-level abstract features from images automatically. Therefore, we introduce it to analyze histopathological images of breast cancer via supervised and unsupervised deep convolutional neural networks. First, we adapted Inception_V3 and Inception_ResNet_V2 architectures to the binary and multi-class issues of breast cancer histopathological image classification by utilizing transfer learning techniques. Then, to overcome the influence from the imbalanced histopathological images in subclasses, we balanced the subclasses with Ductal Carcinoma as the baseline by turning images up and down, right and left, and rotating them counterclockwise by 90 and 180 degrees. Our experimental results of the supervised histopathological image classification of breast cancer and the comparison to the results from other studies demonstrate that Inception_V3 and Inception_ResNet_V2 based histopathological image classification of breast cancer is superior to the existing methods. Furthermore, these findings show that Inception_ResNet_V2 network is the best deep learning architecture so far for diagnosing breast cancers by analyzing histopathological images. Therefore, we used Inception_ResNet_V2 to extract features from breast cancer histopathological images to perform unsupervised analysis of the images. We also constructed a new autoencoder network to transform the features extracted by Inception_ResNet_V2 to a low dimensional space to do clustering analysis of the images. The experimental results demonstrate that using our proposed autoencoder network results in better clustering results than those based on features extracted only by Inception_ResNet_V2 network. All of our experimental results demonstrate that Inception_ResNet_V2 network based deep transfer learning provides a new means of performing analysis of histopathological images of breast cancer.

Multi-label classification of data remains to be a challenging problem. Because of the complexity of the data, it is sometimes difficult to infer information about classes that are not mutually exclusive. For medical data, patients could have symptoms of multiple different diseases at the same time and it is important to develop tools that help to identify problems early. Intelligent health risk prediction models built with deep learning architectures offer a powerful tool for physicians to identify patterns in patient data that indicate risks associated with certain types of chronic diseases. Physical examination records of 110,300 anonymous patients were used to predict diabetes, hypertension, fatty liver, a combination of these three chronic diseases, and the absence of disease (8 classes in total). The dataset was split into training (90%) and testing (10%) sub-datasets. Ten-fold cross validation was used to evaluate prediction accuracy with metrics such as precision, recall, and F-score. Deep Learning (DL) architectures were compared with standard and state-of-the-art multi-label classification methods. Preliminary results suggest that Deep Neural Networks (DNN), a DL architecture, when applied to multi-label classification of chronic diseases, produced accuracy that was comparable to that of common methods such as Support Vector Machines. We have implemented DNNs to handle both problem transformation and algorithm adaption type multi-label methods and compare both to see which is preferable. Deep Learning architectures have the potential of inferring more information about the patterns of physical examination data than common classification methods. The advanced techniques of Deep Learning can be used to identify the significance of different features from physical examination data as well as to learn the contributions of each feature that impact a patient’s risk for chronic diseases. However, accurate prediction of chronic disease risks remains a challenging problem that warrants further studies.

Multi-omics studies, which explore the interactions between multiple types of biological factors, have significant advantages over single-omics analysis for their ability to provide a more holistic view of biological processes, uncover the causal and functional mechanisms for complex diseases, and facilitate new discoveries in precision medicine. However, omics datasets often contain missing values, and in multi-omics study designs it is common for individuals to be represented for some omics layers but not all. Since most statistical analyses cannot be applied directly to the incomplete datasets, imputation is typically performed to infer the missing values. Integrative imputation techniques which make use of the correlations and shared information among multi-omics datasets are expected to outperform approaches that rely on single-omics information alone, resulting in more accurate results for the subsequent downstream analyses. In this review, we provide an overview of the currently available imputation methods for handling missing values in bioinformatics data with an emphasis on multi-omics imputation. In addition, we also provide a perspective on how deep learning methods might be developed for the integrative imputation of multi-omics datasets.

In silico toxicity prediction plays an important role in the regulatory decision making and selection of leads in drug design as in vitro/vivo methods are often limited by ethics, time, budget, and other resources. Many computational methods have been employed in predicting the toxicity profile of chemicals. This review provides a detailed end-to-end overview of the application of machine learning algorithms to Structure-Activity Relationship (SAR)-based predictive toxicology. From raw data to model validation, the importance of data quality is stressed as it greatly affects the predictive power of derived models. Commonly overlooked challenges such as data imbalance, activity cliff, model evaluation, and definition of applicability domain are highlighted, and plausible solutions for alleviating these challenges are discussed.

The specificity of toxicant-target biomolecule interactions lends to the very imbalanced nature of many toxicity datasets, causing poor performance in Structure–Activity Relationship (SAR)-based chemical classification. Undersampling and oversampling are representative techniques for handling such an imbalance challenge. However, removing inactive chemical compound instances from the majority class using an undersampling technique can result in information loss, whereas increasing active toxicant instances in the minority class by interpolation tends to introduce artificial minority instances that often cross into the majority class space, giving rise to class overlapping and a higher false prediction rate. In this study, in order to improve the prediction accuracy of imbalanced learning, we employed SMOTEENN, a combination of Synthetic Minority Over-sampling Technique (SMOTE) and Edited Nearest Neighbor (ENN) algorithms, to oversample the minority class by creating synthetic samples, followed by cleaning the mislabeled instances. We chose the highly imbalanced Tox21 dataset, which consisted of 12 in vitro bioassays for > 10,000 chemicals that were distributed unevenly between binary classes. With Random Forest (RF) as the base classifier and bagging as the ensemble strategy, we applied four hybrid learning methods, i.e., RF without imbalance handling (RF), RF with Random Undersampling (RUS), RF with SMOTE (SMO), and RF with SMOTEENN (SMN). The performance of the four learning methods was compared using nine evaluation metrics, among which F₁ score, Matthews correlation coefficient and Brier score provided a more consistent assessment of the overall performance across the 12 datasets. The Friedman’s aligned ranks test and the subsequent Bergmann-Hommel post hoc test showed that SMN significantly outperformed the other three methods. We also found that a strong negative correlation existed between the prediction accuracy and the imbalance ratio (IR), which is defined as the number of inactive compounds divided by the number of active compounds. SMN became less effective when IR exceeded a certain threshold (e.g., > 28). The ability to separate the few active compounds from the vast amounts of inactive ones is of great importance in computational toxicology. This work demonstrates that the performance of SAR-based, imbalanced chemical toxicity classification can be significantly improved through the use of data rebalancing.

Reference genome selection is a prerequisite for successful analysis of next generation sequencing (NGS) data. Current practice employs one of the two most recent human reference genome versions: HG19 or HG38. To date, the impact of genome version on SNV identification has not been rigorously assessed. We conducted analysis comparing the SNVs identified based on HG19 vs HG38, leveraging whole genome sequencing (WGS) data from the genome-in-a-bottle (GIAB) project. First, SNVs were called using 26 different bioinformatics pipelines with either HG19 or HG38. Next, two tools were used to convert the called SNVs between HG19 and HG38. Lastly we calculated conversion rates, analyzed discordant rates between SNVs called with HG19 or HG38, and characterized the discordant SNVs. The conversion rates from HG38 to HG19 (average 95%) were lower than the conversion rates from HG19 to HG38 (average 99%). The conversion rates varied slightly among the various calling pipelines. Around 1.5% SNVs were discordantly converted between HG19 or HG38. The conversions from HG38 to HG19 had more SNVs which failed conversion and more discordant SNVs than the opposite conversion (HG19 to HG38). Most of the discordant SNVs had low read depth, were low confidence SNVs as defined by GIAB, and/or were predominated by G/C alleles (52% observed versus 42% expected). A significant number of SNVs could not be converted between HG19 and HG38. Based on careful review of our comparisons, we recommend HG38 (the newer version) for NGS SNV analysis. To summarize, our findings suggest caution when translating identified SNVs between different versions of the human reference genome.