* Neighborhood: Similar genomic context in different species suggest a similar function of the proteins.
* Fusion-fission events: Proteins that are fused in some genomes are very likely to be functionally linked (as in other genomes where the genes are not fused).
* Occurrence: Proteins that have a similar function or an occurrence in the same metabolic pathway, must be expressed together and have similar phylogenetic profile.
* Coexpression: Predicted association between genes based on observed patterns of simultaneous expression of genes.