Predictions of Protein-Protein Interactions in Schistosoma Mansoni

Abstract

AbstractBackgroundSchistosoma mansoni invasion of the human host involves a variety of cross-species protein-protein interactions. The pathogen expresses a diverse arsenal of proteins that facilitate the breach of physical and biochemical barriers present in skin, evasion of the immune system, and digestion of human hemoglobin, allowing schistosomes to reside in the host for years. However, only a small number of specific interactions between S. mansoni and human proteins have been identified. We present and apply a protocol that generates testable predictions of S. mansoni-human protein interactions.MethodsIn this study, we first predict S. mansoni-human protein interactions based on similarity to known protein complexes. Putative interactions were then scored and assessed using several contextual filters, including the use of annotation automatically derived from literature using a simple natural language processing methodology. Our method predicted 7 out of the 10 previously known cross-species interactions.ConclusionsSeveral predictions that warrant experimental follow-up were presented and discussed, including interactions involving potential vaccine candidate antigens, protease inhibition, and immune evasion. The application framework provides an integrated methodology for investigation of host-pathogen interactions and an extensive source of orthogonal data for experimental analysis. We have made the predictions available online for community perusal.Author SummaryThe S. mansoni parasite is the etiological agent of the disease Schistomiasis. However, protein-protein interactions have been experimentally characterized that relate to pathogenesis and establishment of infection. As with many pathogens, the understanding of these interactions is a key component for the development of new vaccines. In this project, we have applied a computational whole-genome comparative approach to aid in the prediction of interactions between S. mansoni and human proteins and to identify important proteins involved in infection. The results of applying this method recapitulate several previously characterized interactions, as well as suggest additional ones as potential therapeutic targets.