Homology-Based PPI Validation. Concept of homology-based PPI validation: based on an experimentally observed physical interaction between two proteins, X and Y (the questioned 'source' PPI), homologs of both proteins are identified, for example by local sequence alignments. These homologs include both paralogs from within the same species and orthologs from other species. An interaction between a homolog of X and a homolog of Y is called a 'homologous PPI'. If an experimentally observed homologous PPI is found (thick lines), confidence in the questioned source PPI increases.