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

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.

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.

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.