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In Journal of molecular biology ; h5-index 65.0

Infectious diseases in humans appear to be one of the most primary public health issues. Identification of novel disease-associated proteins will furnish an efficient recognition of the novel therapeutic targets. Here, we develop a Graph Convolutional Network (GCN)-based model called PINDeL to identify the disease-associated host proteins by integrating the human Protein Locality Graph and its corresponding topological features. Because of the amalgamation of GCN with the protein interaction network, PINDeL achieves the highest accuracy of 83.45%while AUROC and AUPRC values are 0.90and 0.88, respectively. With high accuracy, recall, F1-score, specificity, AUROC, and AUPRC, PINDeL outperforms other existing machine-learning and deep-learning techniques for disease gene/protein identification in humans. Application of PINDeL on an independent dataset of 24320proteins, which are not used for training, validation, or testing purposes, predicts 6448new disease-protein associations of which we verify 3196disease-proteins through experimental evidence like disease ontology, Gene Ontology, and KEGG pathway enrichment analyses. Our investigation informs that experimentally-verified 748proteins are indeed responsible for pathogen-host protein interactions of which 22disease-proteins share their association with multiple diseases such as cancer, aging, chem-dependency, pharmacogenomics, normal variation, infection, and immune-related diseases. This unique Graph Convolution Network-based prediction model is of utmost use in large-scale disease-protein association prediction and hence, will provide crucial insights on disease pathogenesis and will further aid in developing novel therapeutics.

Das Barnali, Mitra Pralay

2021-Jul-14

Deep Learning-based Classification, Disease-associated Proteins, Enrichment analysis, Graph Convolutional Networks, Topological features of Protein Locality Graph