Transcript Ontologies for Gene Expression and Phenotypes

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Linking Animal
Models to Human Diseases
Supported by NIH P41 HG002659 and U54 HG004028
the University of Oregon, Eugene, OR
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ZFIN:
FlyBase:
Melissa Haendel
Micael Ashburner
Doug Howe
Rachel Drysdale
Erik Segerdell
George Gkoutos
Sierra Taylor
1. Goals
• Annotate mutant phenotypes
• Identify human disease models
2. Strategy
3. Progress
QuickT ime™ and a
T IFF (LZW) decompressor
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Animal disease models:
Humans
Animal models
Mutant Gene
Mutant Gene
Mutant or missing
Protein
Mutant or missing
Protein
Mutant Phenotype
(disease)
Mutant Phenotype
(disease model)
QuickT ime™ and a
T IFF (LZW) decompressor
are needed to see t his picture.
Animal disease models:
Humans
Animal models
Mutant Gene
Mutant Gene
Mutant or missing
Protein
Mutant or missing
Protein
Mutant Phenotype
(disease)
Mutant Phenotype
(disease model)
QuickT ime™ and a
T IFF (LZW) decompressor
are needed to see t his picture.
Animal 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 mutant phenotypes
• Identify human disease models
2. Strategy
3. Progress
Phenotype
(clinical sign) =
entity
+ attribute
+ value
+ placement
+ hypoteloric
P1
= eye
P2
P3
= midface + development + hypoplastic
+ hypertrophied
= kidney + size
shh-/(holoprosencephaly)
Phenotype
(clinical sign) =
entity
+ attribute
+ value
Anatomical ontology
Cell & tissue ontology
Developmental ontology
Gene ontology
biological process
molecular function
cellular component
+
PATO
(phenotype and trait ontology)
Phenotype
(clinical sign) =
entity
+ attribute
+ value
+ placement
+ hypoteloric
P1
= eye
P2
P3
= midface + development + hypoplastic
+ hypertrophied
= kidney + size
Syndrome = P1 + P2 + P3
(disease)
= holoprosencephaly
Human holoprosencephaly
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 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
OMIM
gene
ZFIN
gene
LAMB1
lamb1
FECH
FlyBase
gene
FlyBase
mut pub
ZFIN
mut pub
mouse
LanB1
5
15
fech
Ferrochelatase
2
GLI2
gli2a
ci
SLC4A1
slc4a1
MYO7A
rat
sno
med
OMIM disease
4
39
-
5
9
29
Protoporphyria, Erythropoietic
388
41
27
22
-
CG8177
7
7
7
19
Renal Tubular Acidosis, RTADR
myo7a
ck
84
5
25
16
Deafness; DFNB2; DFNA11
ALAS2
alas2
Alas
1
7
1
14
Anemia, Sideroblastic, X-Linked
KCNH2
kcnh2
sei
27
3
1
12
-
MYH6
myh6
Mhc
166
3
6
12
Cardiomyopathy, Familial
Hypertrophic; CMH
TP53
tp53
p53
64
3
380
19
11
Breast Cancer
ATP2A1
atp2a1
Ca-P60A
32
6
1
1
11
Brody Myopathy
EYA1
eya1
eya
251
5
8
6
Branchiootorenal Dysplasia
SOX10
sox10
Sox100B
1
17
17
4
Waardenburg-Shah Syndrome
3
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
end_stage
(where stages are stored
in separate ontology)
FlyBase:
stage1
part1
part2
stage 2 …
part1
part2
Entity
eye +
Entity
Attribute
Value
placement + hypoteloric
Attribute
eye + hypoteloric
AO
PATO
Trial
curation
Curator
interface
AO
PATO
Trial
curation
Curator
interface
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
QuickT ime™ and a
T IFF (LZW) decompressor
are needed to see t his picture.
Supported by NIH P41 HG002659 and U54 HG004028
the University of Oregon, Eugene, OR