Roughly a third of the proteins found in S. pneumoniae are unknown and this was determined with two methods. First, a yeast two-hybrid mating protocol was used in order to determine the ratio of proteins with known functions to those with unknown functions. The second method was used in order to accurately predict the functions of the given unknown proteins. This was done by compiling a meta-interactome which helped predict the functions of unknown proteins in S. pneumoniae with evolutionarily conserved bacterial strains that had similarities with pneumonia. These external bacterial strains are defined as orthologous strains to S. pneumoniae.