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How are orthologs calculated?

Ortholog gene groups are calculated by NCBI's Eukaryotic Genome Annotation pipeline for the NCBI Gene dataset using a combination of protein sequence similarity and local synteny information. Orthologous gene relationships may additionally be assigned after manual review by a RefSeq genome curator. Orthology is determined between a genome being annotated and a reference genome, typically human, and the set of pairwise orthologs are tracked as a group. Only genes in the NCBI Gene database are in scope for ortholog calculation. With a few exceptions, the current taxonomic scope for ortholog calculation is limited to vertebrates.