EGeRepDR: An enhanced genetic-based representation learning for drug repurposing using multiple biomedical sources.

MOTIVATION: Drug repurposing (DR) is an imminent approach for identifying novel therapeutic indications for the available drugs and discovering novel drugs for previously untreatable diseases. Nowadays, DR has major attention in the pharmaceutical industry due to the high cost and time of launching new drugs to the market through traditional drug development. DR task majorly depends on genetic information since the drugs revert the modified Gene Expression (GE) of diseases to normal. Many of the existing studies have not considered the genetic importance of predicting the potential candidates. METHOD: We proposed a novel multimodal framework that utilizes genetic aspects of drugs and diseases such as genes, pathways, gene signatures, or expression to enhance the performance of DR using various data sources. Firstly, the heterogeneous biological network (HBN) is constructed with three types of nodes namely drug, disease, and gene, and 4 types of edges similarities (drug, gene, and disease), drug-gene, gene-disease, and drug-disease. Next, a modified graph auto-encoder (GAE*) model is applied to learn the representation of drug and disease nodes using the topological structure and edge information. Secondly, the HBN is enhanced with the information extracted from biomedical literature and ontology using a novel semi-supervised pattern embedding-based bootstrapping model and novel DR perspective representation learning respectively to improve the prediction performance. Finally, our proposed system uses a neural network model to generate the probability score of drug-disease pairs. RESULTS: We demonstrate the efficiency of the proposed model on various datasets and achieved outstanding performance in 5-fold cross-validation (AUC = 0.99, AUPR = 0.98). Further, we validated the top-ranked potential candidates using pathway analysis and proved that the known and predicted candidates share common genes in the pathways.

DRADTiP: Drug repurposing for aging disease through drug-target interaction prediction.

MOTIVATION: The greatest risk factor for many non-communicable diseases is aging. Studies on model organisms have demonstrated that genetic and chemical perturbation alterations can lengthen longevity and overall health. However, finding longevity-enhancing medications and their related targets is difficult. METHOD: In this work, we designed a novel drug repurposing model by identifying the interaction between aging-related genes or targets and drugs similar to aging disease. Each disease is associated with certain specific genetic factors for the occurrence of that disease. The factors include gene expression, pathway, miRNA, and degree of genes in the protein-protein interaction network. In this paper, we aim to find the drugs that prolong the life span of humans with their aging-related targets using the above-mentioned factors. In addition, the contribution or importance of each factor may vary among drugs and targets. Therefore, we designed a novel multi-layer random walk-based network representation learning model including node and edge weight to learn the features of drugs and targets respectively. RESULT: The performance of the proposed model is demonstrated using k-fold cross-validation (k = 5). This model achieved better performance with scores of 0.93 and 0.91 for precision and recall respectively. The drugs identified by the system are evaluated to be potential candidates for aging since the degree of interaction between the potential drugs and their gene sets are high. In addition, the genes that are interacting with drugs produce the same biological functions. Hence the life span of the human will be increased or prolonged.

DTiGNN: Learning drug-target embedding from a heterogeneous biological network based on a two-level attention-based graph neural network.

MOTIVATION: In vitro experiment-based drug-target interaction (DTI) exploration demands more human, financial and data resources. In silico approaches have been recommended for predicting DTIs to reduce time and cost. During the drug development process, one can analyze the therapeutic effect of the drug for a particular disease by identifying how the drug binds to the target for treating that disease. Hence, DTI plays a major role in drug discovery. Many computational methods have been developed for DTI prediction. However, the existing methods have limitations in terms of capturing the interactions via multiple semantics between drug and target nodes in a heterogeneous biological network (HBN). METHODS: In this paper, we propose a DTiGNN framework for identifying unknown drug-target pairs. The DTiGNN first calculates the similarity between the drug and target from multiple perspectives. Then, the features of drugs and targets from each perspective are learned separately by using a novel method termed an information entropy-based random walk. Next, all of the learned features from different perspectives are integrated into a single drug and target similarity network by using a multi-view convolutional neural network. Using the integrated similarity networks, drug interactions, drug-disease associations, protein interactions and protein-disease association, the HBN is constructed. Next, a novel embedding algorithm called a meta-graph guided graph neural network is used to learn the embedding of drugs and targets. Then, a convolutional neural network is employed to infer new DTIs after balancing the sample using oversampling techniques. RESULTS: The DTiGNN is applied to various datasets, and the result shows better performance in terms of the area under receiver operating characteristic curve (AUC) and area under precision-recall curve (AUPR), with scores of 0.98 and 0.99, respectively. There are 23,739 newly predicted DTI pairs in total.

Enhanced disease-disease association with information enriched disease representation.

OBJECTIVE: Quantification of disease-disease association (DDA) enables the understanding of disease relationships for discovering disease progression and finding comorbidity. For effective DDA strength calculation, there is a need to address the main challenge of integration of various biomedical aspects of DDA is to obtain an information rich disease representation. MATERIALS AND METHODS: An enhanced and integrated DDA framework is developed that integrates enriched literature-based with concept-based DDA representation. The literature component of the proposed framework uses PubMed abstracts and consists of improved neural network model that classifies DDAs for an enhanced literature-based DDA representation. Similarly, an ontology-based joint multi-source association embedding model is proposed in the ontology component using Disease Ontology (DO), UMLS, claims insurance, clinical notes etc. Results and Discussion: The obtained information rich disease representation is evaluated on different aspects of DDA datasets such as Gene, Variant, Gene Ontology (GO) and a human rated benchmark dataset. The DDA scores calculated using the proposed method achieved a high correlation mainly in gene-based dataset. The quantified scores also shown better correlation of 0.821, when evaluated on human rated 213 disease pairs. In addition, the generated disease representation is proved to have substantial effect on correlation of DDA scores for different categories of disease pairs. CONCLUSION: The enhanced context and semantic DDA framework provides an enriched disease representation, resulting in high correlated results with different DDA datasets. We have also presented the biological interpretation of disease pairs. The developed framework can also be used for deriving the strength of other biomedical associations.