In this article, we provide a comprehensive introduction to knowledge graphs, which have recently garnered significant attention from both industry and academia in scenarios that require exploiting diverse, dynamic, large-scale collections of data. After some opening remarks, we motivate and contrast various graph-based data models, as well as languages used to query and validate knowledge graphs. We explain how knowledge can be represented and extracted using a combination of deductive and inductive techniques. We conclude with high-level future research directions for knowledge graphs.

Clustering is central to many data-driven bioinformatics research and serves a powerful computational method. In particular, clustering helps at analyzing unstructured and high-dimensional data in the form of sequences, expressions, texts and images. Further, clustering is used to gain insights into biological processes in the genomics level, e.g. clustering of gene expressions provides insights on the natural structure inherent in the data, understanding gene functions, cellular processes, subtypes of cells and understanding gene regulations. Subsequently, clustering approaches, including hierarchical, centroid-based, distribution-based, density-based and self-organizing maps, have long been studied and used in classical machine learning settings. In contrast, deep learning (DL)-based representation and feature learning for clustering have not been reviewed and employed extensively. Since the quality of clustering is not only dependent on the distribution of data points but also on the learned representation, deep neural networks can be effective means to transform mappings from a high-dimensional data space into a lower-dimensional feature space, leading to improved clustering results. In this paper, we review state-of-the-art DL-based approaches for cluster analysis that are based on representation learning, which we hope to be useful, particularly for bioinformatics research. Further, we explore in detail the training procedures of DL-based clustering algorithms, point out different clustering quality metrics and evaluate several DL-based approaches on three bioinformatics use cases, including bioimaging, cancer genomics and biomedical text mining. We believe this review and the evaluation results will provide valuable insights and serve a starting point for researchers wanting to apply DL-based unsupervised methods to solve emerging bioinformatics research problems.

In this paper 1 , we proposed an explainable deep neural networks (DNN)-based method for automatic detection of COVID-19 symptoms from chest radiography (CXR) images, which we call 'DeepCOVIDExplainer'. We used 15,959 CXR images of 15,854 patients, covering normal, pneumonia, and COVID-19 cases. CXR images are first comprehensively preprocessed and augmented before classifying with a neural ensemble method, followed by highlighting class-discriminating regions using gradient-guided class activation maps (Grad-CAM++) and layer-wise relevance propagation (LRP). Further, we provide human-interpretable explanations for the diagnosis. Evaluation results show that our approach can identify COVID-19 cases with a positive predictive value (PPV) of 91.6%, 92.45%, and 96.12%, respectively for normal, pneumonia, and COVID-19 cases, respectively, outperforming recent approaches.

Question answering over knowledge graphs (KGQA) has evolved from simple single-fact questions to complex questions that require graph traversal and aggregation. We propose a novel approach for complex KGQA that uses unsupervised message passing, which propagates confidence scores obtained by parsing an input question and matching terms in the knowledge graph to a set of possible answers. First, we identify entity, relationship, and class names mentioned in a natural language question, and map these to their counterparts in the graph. Then, the confidence scores of these mappings propagate through the graph structure to locate the answer entities. Finally, these are aggregated depending on the identified question type.This approach can be efficiently implemented as a series of sparse matrix multiplications mimicking joins over small local subgraphs. Our evaluation results show that the proposed approach outperforms the state-of-the-art on the LC-QuAD benchmark. Moreover, we show that the performance of the approach depends only on the quality of the question interpretation results, i.e., given a correct relevance score distribution, our approach always produces a correct answer ranking. Our error analysis reveals correct answers missing from the benchmark dataset and inconsistencies in the DBpedia knowledge graph. Finally, we provide a comprehensive evaluation of the proposed approach accompanied with an ablation study and an error analysis, which showcase the pitfalls for each of the question answering components in more detail.

Interference between pharmacological substances can cause serious medical injuries. Correctly predicting so-called drug-drug interactions (DDI) does not only reduce these cases but can also result in a reduction of drug development cost. Presently, most drug-related knowledge is the result of clinical evaluations and post marketing surveillance; resulting in a limited amount of information. Existing data-driven prediction approaches for DDIs typically rely on a single source of information, while using information from multiple sources would help improve predictions. Machine learning (ML) techniques are used, but the techniques are often unable to deal with skew in the data. Hence, we propose a new ML approach for predicting DDIs based on multiple data sources. For this task we use 12,000 drug features from DrugBank, PharmGKB, and KEGG drugs, which are integrated using Knowledge Graphs (KGs). To train our prediction model, we first embed the nodes in the graph using various embedding approaches. We found that the best performing combination was a ComplEx embedding method creating using PyTorch-BigGraph (PBG) with a Convolutional-LSTM network and classic machine learning based prediction models. The model averaging ensemble method of three best classifiers yields up to 0.94, 0.92, 0.80 for AUPR, F1-score, and MCC, respectively during 5-fold cross-validation tests.