FlyBase computes D. melanogaster genes that are relevant to human diseases and reports them as Disease Ontology (DO) annotations by combining three sets of data: (i) D. melanogaster-to-human orthology relationships from the DRSC Integrative Ortholog Prediction Tool (DIOPT) (https://www.flyrnai.org/cgi-bin/DRSC_orthologs.pl); (ii) human gene-to-phenotype relationships within OMIM (https://www.omim.org); and (iii) OMIM phenotype cross-references within the DO (http://disease-ontology.org). The logic flow may be summarized as: D. melanogaster gene -> human ortholog (DIOPT score > 2) -> OMIM phenotype > DO term. (Note that orthology relationships that are supported by only 1 or 2 independent algorithms within DIOPT are ignored in this pipeline.)

These associations are reported as 'Potential Models Based on Orthology' within the 'Human Disease Model Data' section of FlyBase Gene Reports and in the 'human_disease_model' precomputed data file. They are distinguished from DO annotations based on experimental data by having an 'Inferred from Electronic Annotation' (IEA) evidence code.