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MotivationMining drug-disease association and related interactions are essential for developing in silico drug repurposing (DR) methods and understanding underlying biological mechanisms. Recently, large-scale biological databases are increasingly available for pharmaceutical research, allowing for deep characterization for molecular informatics and drug discovery. However, DR is challenging due to the molecular heterogeneity of disease and diverse drug-disease associations. Importantly, the complexity of molecular target interactions, such as protein-protein interaction (PPI), remains to be elucidated. DR thus requires deep exploration of a multimodal biological network in an integrative context.ResultsIn this study, we propose BiFusion, a bipartite graph convolution network model for DR through heterogeneous information fusion. Our approach combines insights of multiscale pharmaceutical information by constructing a multirelational graph of drug-protein, disease-protein and PPIs. Especially, our model introduces protein nodes as a bridge for message passing among diverse biological domains, which provides insights into utilizing PPI for improved DR assessment. Unlike conventional graph convolution networks always assuming the same node attributes in a global graph, our approach models interdomain information fusion with bipartite graph convolution operation. We offered an exploratory analysis for finding novel drug-disease associations. Extensive experiments showed that our approach achieved improved performance than multiple baselines for DR analysis.Availability and implementationSource code and preprocessed datasets are at: https://github.com/zcwang0702/BiFusion.

Summary Mechanistic molecular studies in biomedical research often discover important genes that are aberrantly over- or under-expressed in disease. However, manipulating these genes in an attempt to improve the disease state is challenging. Herein, we reveal Drug Gene Budger (DGB), a web-based and mobile application developed to assist investigators in order to prioritize small molecules that are predicted to maximally influence the expression of their target gene of interest. With DGB, users can enter a gene symbol along with the wish to up-regulate or down-regulate its expression. The output of the application is a ranked list of small molecules that have been experimentally determined to produce the desired expression effect. The table includes log-transformed fold change, P -value and q -value for each small molecule, reporting the significance of differential expression as determined by the limma method. Relevant links are provided to further explore knowledge about the target gene, the small molecule and the source of evidence from which the relationship between the small molecule and the target gene was derived. The experimental data contained within DGB is compiled from signatures extracted from the LINCS L1000 dataset, the original Connectivity Map (CMap) dataset and the Gene Expression Omnibus (GEO). DGB also presents a specificity measure for a drug–gene connection based on the number of genes a drug modulates. DGB provides a useful preliminary technique for identifying small molecules that can target the expression of a single gene in human cells and tissues. Availability and implementation The application is freely available on the web at http://DGB.cloud and as a mobile phone application on iTunes https://itunes.apple.com/us/app/drug-gene-budger/id1243580241? mt=8 and Google Play https://play.google.com/store/apps/details? id=com.drgenebudger. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]