The drug development is generally arduous, costly, and success rates are low. Thus, the identification of drug-target interactions (DTIs) has become a crucial step in early stages of drug discovery. Consequently, developing computational approaches capable of identifying potential DTIs with minimum error rate are increasingly being pursued. These computational approaches aim to narrow down the search space for novel DTIs and shed light on drug functioning context. Most methods developed to date use binary classification to predict if the interaction between a drug and its target exists or not. However, it is more informative but also more challenging to predict the strength of the binding between a drug and its target. If that strength is not sufficiently strong, such DTI may not be useful. Therefore, the methods developed to predict drug-target binding affinities (DTBA) are of great value. In this study, we provide a comprehensive overview of the existing methods that predict DTBA. We focus on the methods developed using artificial intelligence (AI), machine learning (ML), and deep learning (DL) approaches, as well as related benchmark datasets and databases. Furthermore, guidance and recommendations are provided that cover the gaps and directions of the upcoming work in this research area. To the best of our knowledge, this is the first comprehensive comparison analysis of tools focused on DTBA with reference to AI/ML/DL.

In silico prediction of drug–target interactions is a critical phase in the sustainable drug development process, especially when the research focus is to capitalize on the repositioning of existing drugs. However, developing such computational methods is not an easy task, but is much needed, as current methods that predict potential drug–target interactions suffer from high false-positive rates. Here we introduce DTiGEMS+, a computational method that predictsDrug–Targetinteractions usingGraphEmbedding, graphMining, andSimilarity-based techniques. DTiGEMS+ combines similarity-based as well as feature-based approaches, and models the identification of novel drug–target interactions as a link prediction problem in a heterogeneous network. DTiGEMS+ constructs the heterogeneous network by augmenting the known drug–target interactions graph with two other complementary graphs namely: drug–drug similarity, target–target similarity. DTiGEMS+ combines different computational techniques to provide the final drug target prediction, these techniques include graph embeddings, graph mining, and machine learning. DTiGEMS+ integrates multiple drug–drug similarities and target–target similarities into the final heterogeneous graph construction after applying a similarity selection procedure as well as a similarity fusion algorithm. Using four benchmark datasets, we show DTiGEMS+ substantially improves prediction performance compared to other state-of-the-art in silico methods developed to predict of drug-target interactions by achieving the highest average AUPR across all datasets (0.92), which reduces the error rate by 33.3% relative to the second-best performing model in the state-of-the-art methods comparison.

Linked data and bio-ontologies enabling knowledge representation, standardization, and dissemination are an integral part of developing biological and biomedical databases. That is, linked data and bio-ontologies are employed in databases to maintain data integrity, data organization, and to empower search capabilities. However, linked data and bio-ontologies are more recently being used to represent information as multi-relational heterogeneous graphs, “knowledge graphs”. The reason being, entities and relations in the knowledge graph can be represented as embedding vectors in semantic space, and these embedding vectors have been used to predict relationships between entities. Such knowledge graph embedding methods provide a practical approach to data analytics and increase chances of building machine learning models with high prediction accuracy that can enhance decision support systems. Here, we present a comparative assessment and a standard benchmark for knowledge graph-based representation learning methods focused on the link prediction task for biological relations. We systematically investigated and compared state-of-the-art embedding methods based on the design settings used for training and evaluation. We further tested various strategies aimed at controlling the amount of information related to each relation in the knowledge graph and its effects on the final performance. We also assessed the quality of the knowledge graph features through clustering and visualization and employed several evaluation metrics to examine their uses and differences. Based on this systematic comparison and assessments, we identify and discuss the limitations of knowledge graph-based representation learning methods and suggest some guidelines for the development of more improved methods.

The accurate identification of the exon/intron boundaries is critical for the correct annotation of genes with multiple exons. Donor and acceptor splice sites (SS) demarcate these boundaries. Therefore, deriving accurate computational models to predict the SS are useful for functional annotation of genes and genomes, and for finding alternative SS associated with different diseases. Although various models have been proposed for the in silico prediction of SS, improving their accuracy is required for reliable annotation. Moreover, models are often derived and tested using the same genome, providing no evidence of broad application, i.e. to other poorly studied genomes. With this in mind, we developed the Splice2Deep models for SS detection. Each model is an ensemble of deep convolutional neural networks. We evaluated the performance of the models based on the ability to detect SS in Homo sapiens, Oryza sativa japonica, Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans. Results demonstrate that the models efficiently detect SS in other organisms not considered during the training of the models. Compared to the state-of-the-art tools, Splice2Deep models achieved significantly reduced average error rates of 41.97% and 28.51% for acceptor and donor SS, respectively. Moreover, the Splice2Deep cross-organism validation demonstrates that models correctly identify conserved genomic elements enabling annotation of SS in new genomes by choosing the taxonomically closest model. The results of our study demonstrated that Splice2Deep both achieved a considerably reduced error rate compared to other state-of-the-art models and the ability to accurately recognize SS in other organisms for which the model was not trained, enabling annotation of poorly studied or newly sequenced genomes. Splice2Deep models are implemented in Python using Keras API; the models and the data are available at https://github.com/SomayahAlbaradei/Splice_Deep.git.

Reliable quantification of cellular treatment effects in many bioassays depends on the accuracy of cell colony counting. However, colony counting processes tend to be tedious, slow, and error-prone. Thus, pursuing an effective colony counting technique is ongoing, and varies from manual approaches to partly automated and fully automated techniques. Most fully automated techniques were developed using deep learning (DL). A significant problem in applying DL to this task is the lack of sizeable collections of annotated plate images. For this reason, here we propose an application of Transfer Learning to cell colony counting that can overcome this problem by exploiting models trained for other tasks. To demonstrate this idea's feasibility, we show how a small dataset can be used to transform a DL model designed for counting objects in congested scenes into a specialized cell colony counting model and achieve better performance than existing, more widely-used models.