Linking Animal Models to Human Diseases Supported by NIH P41 HG and U54 HG the University of Oregon, Eugene, OR

ZFIN: Melissa Haendel Doug Howe Erik Segerdell Sierra Taylor FlyBase: Micael Ashburner Rachel Drysdale George Gkoutos

1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

HumansAnimal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Gene Mutant or missing Protein Mutant Phenotype (disease model) Animal disease models:

HumansAnimal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Gene Mutant or missing Protein Mutant Phenotype (disease model) Animal disease models:

HumansAnimal models Mutant Gene Mutant or missing Protein Mutant Phenotype (disease) Mutant Gene Mutant or missing Protein Mutant Phenotype (disease model) Animal disease models:

1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

eyeplacementhypoteloric++ entityvalueattribute++ midfacedevelopmenthypoplastic+ + kidneysizehypertrophied+ + Phenotype (clinical sign) = P 1 = P 2 = P 3 = shh -/- (holoprosencephaly)

entityvalueattribute++ Phenotype (clinical sign) = Anatomical ontology Cell & tissue ontology Developmental ontology Gene ontology biological process molecular function cellular component + PATO (phenotype and trait ontology)

eyeplacementhypoteloric++ entityvalueattribute++ midfacedevelopmenthypoplastic+ + kidneysizehypertrophied+ + Phenotype (clinical sign) = P 1 = P 2 = P 3 = Syndrome = P 1 + P 2 + P 3 (disease) = holoprosencephaly

Human holo- prosencephaly Zebrafish shh Zebrafish oep

1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

OMIM genes ZFIN mutant genes FlyBase mutant genes

Data type Total Total ZFIN genes20,385 Genes with assigned human orthologs2,884 Genes with OMIM links2,174 Total ZFIN mutants3,188 ZFIN mutants with OMIM links Corresponding human genes Drosophila homologs of these

OMIM gene ZFIN gene FlyBase gene FlyBase mut pub ZFIN mut pub mouseratsno med OMIM disease LAMB1lamb1LanB FECHfechFerro- chelatase Protoporphyria, Erythropoietic GLI2gli2aci SLC4A1slc4a1CG Renal Tubular Acidosis, RTADR MYO7Amyo7ack Deafness; DFNB2; DFNA11 ALAS2alas2Alas17114 Anemia, Sideroblastic, X-Linked KCNH2kcnh2sei MYH6myh6Mhc Cardiomyopathy, Familial Hypertrophic; CMH TP53tp53p Breast Cancer ATP2A1atp2a1Ca-P60A Brody Myopathy EYA1eya1eya Branchiootorenal Dysplasia SOX10sox10Sox100B117 4 Waardenburg-Shah Syndrome

PATO development (underway) : Curator interface development (underway) Trial curation of ZFIN & FlyBase publications + OMIM (future)

PATO development (underway) : Anatomical Ontology cleanup PATO cleanup Curator interface development (underway) Trial curation of ZFIN & FlyBase publications + OMIM (future)

Resolving AO differences between ZFIN and FlyBase ZFIN: part start_stage (where stages are stored end_stage in separate ontology) FlyBase: stage1stage 2 … part1 part2

eyeplacementhypoteloric+ + eye hypoteloric+ EntityAttributeValue EntityAttribute

AO PATO Curator interface Trial curation

AO PATO Curator interface Trial curation User interface

PATO development (underway) : Anatomical Ontology cleanup PATO cleanup Initial curation of fish phenotypes - portable database for research labs CToL - taxonomy & phylogenies Curator interface development (underway) Trial curation of ZFIN & FlyBase publications + OMIM (future)

1.Goals Annotate mutant phenotypes Identify human disease models 2.Strategy 3.Progress

Supported by NIH P41 HG and U54 HG the University of Oregon, Eugene, OR