Hybrid Deep Learning Based on a Heterogeneous Network Profile for Functional Annotations of Plasmodium falciparum Genes

Abstract

Functional annotation of unknown function genes reveals unidentified functions that can enhance our understanding of complex genome communications. A common approach for inferring gene function involves the ortholog-based method. However, genetic data alone are often not enough to provide information for function annotation. Thus, integrating other sources of data can potentially increase the possibility of retrieving annotations. Network-based methods are efficient techniques for exploring interactions among genes and can be used for functional inference. In this study, we present an analysis framework for inferring the functions of Plasmodium falciparum genes based on connection profiles in a heterogeneous network between human and Plasmodium falciparum proteins. These profiles were fed into a hybrid deep learning algorithm to predict the orthologs of unknown function genes. The results show high performance of the model’s predictions, with an AUC of 0.89. One hundred and twenty-one predicted pairs with high prediction scores were selected for inferring the functions using statistical enrichment analysis. Using this method, PF3D7_1248700 and PF3D7_0401800 were found to be involved with muscle contraction and striated muscle tissue development, while PF3D7_1303800 and PF3D7_1201000 were found to be related to protein dephosphorylation. In conclusion, combining a heterogeneous network and a hybrid deep learning technique can allow us to identify unknown gene functions of malaria parasites. This approach is generalized and can be applied to other diseases that enhance the field of biomedical science.