Workflow of the HaMStR approach. Standard orthology prediction tools are used to identify orthologous groups, the so called core-orthologs, for a set of completely sequenced primer taxa (Proteome A - F). The sequences in a core-ortholog are aligned and converted into a profile HMM (pHMM). A compilation of protein sequences or translated ESTs from a taxon not included in the primer-taxa (Protein set G) is searched for hits with the pHMM. The resulting candidates display features that are characteristic for the protein modelled by the pHMM. To determine the orthology status of the candidates, we introduce a reciprocity criterion. Each candidate is compared by BLASTP with the proteome of one of the primer-taxa, the so-called reference-taxon (Proteome F). If the best BLASTP hit sequence from the reference taxon corresponds to the protein that contributed to the pHMM, the candidate is called candidate-ortholog, else it is discarded.