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BackGround Bacterial genomes are being deposited into online databases at an increasing rate. Genome annotation represents one of the first efforts to understand organisms and their diseases. Some evolutionary relationships capable of being annotated only from genomes are conserved gene neighbourhoods (CNs), phylogenetic profiles (PPs), and gene fusions. At present, there is no standalone software that enables networks of interactions among proteins to be created using these three evolutionary characteristics with efficient and effective results. Results We developed GENPPI software for the ab initio prediction of interaction networks using predicted proteins from a genome. In our case study, we employed 50 genomes of the genus  Corynebacterium . Based on the PP relationship, GENPPI differentiated genomes between the ovis and equi biovars of the species  Corynebacterium pseudotuberculosis  and created groups among the other species analysed. If we inspected only the CN relationship, we could not entirely separate biovars, only species. Our software GENPPI was determined to be efficient because, for example, it creates interaction networks from the central genomes of 50 species/lineages with an average size of 2200 genes in less than 40 min on a conventional computer. Moreover, the interaction networks that our software creates reflect correct evolutionary relationships between species, which we confirmed with average nucleotide identity analyses. Additionally, this software enables the user to define how he or she intends to explore the PP and CN characteristics through various parameters, enabling the creation of customized interaction networks. For instance, users can set parameters regarding the genus, metagenome, or pangenome. In addition to the parameterization of GENPPI, it is also the user’s choice regarding which set of genomes they are going to study. Conclusions GENPPI can help fill the gap concerning the considerable number of novel genomes assembled monthly and our ability to process interaction networks considering the noncore genes for all completed genome versions. With GENPPI, a user dictates how many and how evolutionarily correlated the genomes answer a scientific query.

GENPPI: standalone software for creating protein interaction networks from genomes