Tracking the functional meaning of the human oral-microbiome protein-protein interactions

Adv Protein Chem Struct Biol. 2020:121:199-235. doi: 10.1016/bs.apcsb.2019.11.014. Epub 2020 Jan 16.

Abstract

The interactome - the network of protein-protein interactions (PPIs) within a cell or organism - is technically difficult to assess. Bioinformatic tools can, not only, identify potential PPIs that can be later experimentally validated, but also be used to assign functional meaning to PPIs. Saliva's potential as a non-invasive diagnostic fluid is currently being explored by several research groups. But, in order to fully attain its potential, it is necessary to achieve the full characterization of the mechanisms that take place within this ecosystem. The onset of omics technologies, and specifically of proteomics, delivered a huge set of data that is largely underexplored. Quantitative information relative to proteins within a given context (for example a given disease) can be used by computational algorithms to generate information regarding PPIs. These PPIs can be further analyzed concerning their functional meaning and used to identify potential biomarkers, therapeutic targets, defense and pathogenicity mechanisms. We describe a computational pipeline that can be used to identify and analyze PPIs between human and microbial proteins. The pipeline was tested within the scenario of human PPIs of systemic (Zika Virus infection) and of oral conditions (Periodontal disease) and also in the context of microbial interactions (Candida-Streptococcus) and showed to successfully predict functionally relevant PPIs. The pipeline can be applied to different scientific areas, such as pharmacological research, since a functional meaningful PPI network can provide insights on potential drug targets, and even new uses for existing drugs on the market.

Keywords: Drug targets; Host-microbial interactomics; In silico interactomics; Oral microbial targets; PPIs in saliva; Saliva diagnostics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism*
  • Biomarkers / metabolism
  • Dental Caries / genetics
  • Dental Caries / immunology
  • Dental Caries / metabolism
  • Dental Caries / microbiology*
  • Fungal Proteins / immunology
  • Fungal Proteins / metabolism*
  • Gingivitis / genetics
  • Gingivitis / immunology
  • Gingivitis / metabolism
  • Gingivitis / microbiology*
  • Host-Pathogen Interactions
  • Humans
  • Microbiota / immunology
  • Mouth / immunology
  • Mouth / metabolism
  • Mouth / microbiology*
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / immunology
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / microbiology
  • Peri-Implantitis / genetics
  • Peri-Implantitis / immunology
  • Peri-Implantitis / metabolism
  • Peri-Implantitis / microbiology
  • Periodontitis / genetics
  • Periodontitis / immunology
  • Periodontitis / metabolism
  • Periodontitis / microbiology*
  • Precancerous Conditions / genetics
  • Precancerous Conditions / immunology
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / microbiology
  • Protein Interaction Mapping
  • Proteomics / methods
  • Salivary Proteins and Peptides / immunology
  • Salivary Proteins and Peptides / metabolism*

Substances

  • Bacterial Proteins
  • Biomarkers
  • Fungal Proteins
  • Salivary Proteins and Peptides