Wuchty et al. (2017)
The Protein Interactome of Streptococcus pneumoniae and
Bacterial Meta-interactomes Improve Function Predictions.
mSystems 2:1-10

(Translated by Karun Rajesh)

Support: Ortholog Determination

Orthologs are a key part of this paper, as they serve as the linking connection between different bacterial species. Orthologs are genes in different species that evolved from a common ancestor. In order to determine orthologous proteins between different bacteria, as described in this paper, a program called BLASTp must be used.

A given set of proteins that we want to find out the function of is inputted into this program along with a set of proteins from a different bacterium. BLASTp then compares the amino acid sequence between these proteins one by one and determines for one protein the ranking of which protein is most closely related to it in the other bacterium. The order of the proteins inputted into the program is then reversed. If the protein ranked #1 for a functionally unknown protein then has that same functionally unknown protein ranked #1 for itself, then the proteins are determined to be orthologs of one another.

There then leads to two possibilities of how this knowledge can be used. If the orthologous protein in another bacterium has a known function, then it becomes a simple one to one match. The function of this protein is then assigned to the functionally unknown protein and that is its defined function. Figure 1 illustrates this concept.

The other possibility is if the orthologous protein does not have a known function. If the function is not known, then there are additional steps that need to be taken. First, the protein interactions of the orthologous protein need to be found. These interactions are then applied to the functionally unknown protein, in hopes that these extra interactions will be able to give a clearer picture of what type of proteins this unknown protein interacts with. Figure 2 illustrates this concept.

Fig. 9: Unknown Ortholog If the ortholog does not have a known function. If the function is not known, then there are additional steps that need to be taken.

Fig. 10: Unknown Ortholog Continuation of Figure 7.