Inter-Species/Host-Parasite Protein Interaction Predictions Reviewed

Background: Host-parasite protein interactions (HPPI) are those interactions occurring between a parasite and its host. Host-parasite protein interaction enhances the understanding of how parasite can infect its host. The interaction plays an important role in initiating infections, although it is not all host-parasite interactions that result in infection. Identifying the protein-protein interactions (PPIs) that allow a parasite to infect its host has a lot do in discovering possible drug targets. Such PPIs, when altered, would prevent the host from being infected by the parasite and in some cases, result in the parasite inability to complete specific stages of its life cycle and invariably lead to the death of such parasite. It therefore becomes important to understand the workings of host-parasite interactions which are the major causes of most infectious diseas

Bioinformatic pipelines to reconstruct and analyse intercellular and hostmicrobe interactions affecting epithelial signalling pathways

The epithelium segregates microorganisms from the immune system through tightly connected cells. The epithelial barrier maintains the integrity of the body, and the microbiome influences this through host-microbe interactions. Therefore its composition has an impact on the host's physiological processes. Disruption in the microbiome composition leads to an impaired epithelial layer. As a consequence, the cell-cell interactions between the epithelium and immune cells will be altered, contributing to inflammation. In this thesis, I examined the interconnectivity of the microbiome, epithelium and immune system in the gastrointestinal tract focusing on the oral cavity and gut in healthy and diseased conditions. I combined multi-omics data with network biology approaches to develop computational pipelines to study host-microbe and cell-cell connections. I used network propagation algorithms to reconstruct intracellular signalling and identify downstream pathways affected by the altered microbiome composition or cell-cell connections. I studied inflammation-related conditions in the oral cavity (periodontitis) and gut (inflammatory bowel disease (IBD)) to reveal the contribution of interspecies and intercellular interactions to diseases. I inferred hostmicrobe protein-protein interaction (HM-PPI) networks between healthy gum-/periodontitisrelated bacteria communities and epithelium, and found altered HM-PPIs during inflammation. I connected the epithelial cells to dendritic cells and identified the Toll-like receptor (TLR) pathway as a potential driver of the inflammation in diseased gingiva. While in the oral cavity I focused on complex microbial communities and their impact on one cell type, I discovered the direct effect of gut commensal bacteria on several immune cells in IBD. This study observed the cell-specific effect of Bacteroides thetaiotaomicron on TLR signalling. The pipelines I developed offer potentially interesting connections that aid detailed mechanistic insight into the relationship between the microbiome, epithelial barrier and immune system. These systems-level analysis tools facilitate the understanding of how microbial proteins may be of therapeutic value in inflammatory diseases