Download Ontologies for Gene Expression and Phenotypes

Linking Animal
Models to Human Diseases
Supported by NIH P41 HG002659 and U54 HG002659
the University of Oregon, Eugene, OR
http://zfin.org
1. Goals
•
•
Annotate zebrafish phenotypes
Identify human disease models
2. Example holoprosencephaly
3. Progress
Zebrafish disease models:
Animal models
Mutant Gene
Mutant or
missing Protein
Mutant Phenotype
Zebrafish disease models:
Humans
Animal models
Mutant Gene
Mutant Gene
Mutant or
missing Protein
Mutant or
missing Protein
Mutant Phenotype
(disease)
Mutant Phenotype
(disease model)
Zebrafish disease models:
Humans
Animal models
Mutant Gene
Mutant Gene
Mutant or
missing Protein
Mutant or
missing Protein
Mutant Phenotype
(disease)
Mutant Phenotype
(disease model)
Zebrafish disease models:
Humans
Animal models
Mutant Gene
Mutant Gene
Mutant or
missing Protein
Mutant or
missing Protein
Mutant Phenotype
(disease)
Mutant Phenotype
(disease model)
1. Goals
•
•
Annotate zebrafish phenotypes
Identify human disease models
2. Example holoprosencephaly
3. Progress
SHH-/+
SHH-/-
shh-/+
shh-/-
Phenotypic
character
= entity
+ attribute
+ value
Phenotypic
character
PC1
= entity
= eye
+ attribute
+ value
+ placement + mislocalized
Phenotypic
character
PC1
PC2
= entity
+ attribute
+ value
= eye
+ placement + mislocalized
= midface + structure + hypoplastic
Phenotypic
character
PC1
PC2
PC3
=
=
=
=
entity
eye
midface
kidney
+
+
+
+
attribute
placement
structure
size
+
+
+
+
value
mislocalized
hypoplastic
hypertrophied
Phenotypic
character
PC1
PC2
PC3
=
=
=
=
entity
eye
midface
kidney
+
+
+
+
attribute
placement
structure
size
ZFIN:
entity = eye
entity = midface
entity = kidney
+
+
+
+
+
value
mislocalized
hypoplastic
hypertrophied
PATO:
attribute = placement
value = mislocalized
attribute = structure
value = hypoplastic
attribute = size
value = hypertrophied
Phenotypic
character = entity + attribute + value
Anatomical ontology
Cell & tissue ontology
Developmental ontology
Gene ontology
biological process
molecular function
cellular component
+
PATO
Phenotypic
character
PC1
PC2
PC3
=
=
=
=
entity
eye
midface
kidney
+
+
+
+
attribute
placement
structure
size
Syndrome
(or disease) = PC1 + PC2 + PC3
= holoprosencephaly
+
+
+
+
value
mislocalized
hypoplastic
hypertrophied
Human holoprosencephaly
Human gene:SHH;OMIM:600725
Ref: OMIM:142945
Entity:prosencephalon development
Attribute:process
Value:arrested
Entity:brain
Attribute:size
Value:small
Entity:brain ventricle
Attribute:number
Value:single
Entity:midface
Attribute:structure
Value:hypoplastic
Entity:eye
Attribute:morphology
Value:abnormal
Entity:eye
Attribute:number
Value:single
Entity:eye
Attribute:placement
Value:mislocalized
Entity:nose
Attribute:morphology
Value:abnormal
Entity:nostril
Attribute:number
Value:single
Entity:kidney
Attribute:rel_size
Value:hypertrophied
Zebrafish
shh
Zebrafish gene:shh
Ref: ZDB-GENE-980526-166
Entity:prosencephalon development
Attribute:process
Value:reduced
Entity:brain
Attribute:size
Value:small
Entity:midface
Attribute:structure
Value:hypoplastic
Entity:eye
Attribute:morphology
Value:abnormal
Entity:eye
Attribute:placement
Value:mislocalized
Entity:kidney
Attribute:rel_size
Value:hypertrophied
Zebrafish
oep
Zebrafish gene:oep
Ref: ZDB-GENE-990415-198
Entity:prosencephalon development
Attribute:process
Value:arrested
Entity:brain
Attribute:size
Value:small
Entity:brain ventricle
Attribute:number
Value:single
Entity:midface
Attribute:structure
Value:hypoplastic
Entity:eye
Attribute:morphology
Value:abnormal
Entity:eye
Attribute:number
Value:single
Entity:eye
Attribute:placement
Value:mislocalized
Entity:nose
Attribute:morphology
Value:abnormal
Entity:nostril
Attribute:number
Value:single
Entity:kidney
Attribute:rel_size
Value:hypertrophied
1. Goals
•
•
Annotate zebrafish phenotypes
Identify human disease models
2. Example holoprosencephaly
3. Progress
ZFIN
mutant
genes
OMIM
genes
ZFIN
mutant
genes
OMIM
genes
ZFIN
mutant
genes
FlyBase
mutant
genes
Data type
Total ZFIN genes
Genes with assigned human orthologs
Genes with OMIM links
Total ZFIN mutants
ZFIN mutants with OMIM links
Corresponding human genes
Drosophila homologs of these 271
Total
20,385
2,884
2,174
3,188
720
271
187
PATO development:
1. Test curation of zebrafish publications
2. Initial curation of phenotypes
•
200 zebrafish mutations(Tübingen, MIT)
•
Morpholino phenotypes (Univ. of Minnesota)
•
400 Medaka mutations (Kyoto)
3. CToL - taxonomy & phylogenies
4. OBO-discuss email list for discussions
http://zfin.org
Melissa Haendel -anatomy ontology
Doug Howe - GO
Erik Segerdell - PATO
Sierra Taylor - database schema
Supported by NIH P41 HG002659 and U54 HG002659
University of Oregon, Eugene, Oregon