Melissa Haendel

1
Melissa Haendel Projects 1. Anatomy and
phenotype ontology curator at Zebrafish
Information Network (ZFIN) 2. The Common Anatomy
Reference Ontology (CARO) 3. Linking animal
models and human disease using ontologies in Open
Biological Database (OBD)
2
Why we build anatomy ontologies (AOs)
Model organism databases (MODs) gene expression
and phenotypes
bmp2b expression
ctcf -/- phenotype
Entity (AO) tail Quality (PATO) curved
Entities otic vesicle, cardinal vein, retina
Evolutionary biologists recording character
states
Gyrinocheilus
Danio rerio
Entity (AO) ceratobranchial 5 tooth Quality
(PATO) is_present
Entity (AO) ceratobranchial 5 tooth Quality
(PATO) is_absent
3
Advantages of using anatomy ontologies for
expression, phenotype and character recording
Terms with written definitions More consistent
annotation despite variable terminology
Stomach?
Logically defined relations between types
Allows annotations to be grouped
finger part_of hand
4
Common Anatomy Reference ontology (CARO) aims to
standardize anatomy ontologies
CARO is a single-inheritance structural
classification based on granularity From the
bottom up Cell component Cell Portion of
tissue Multi-tissue structure From the top
down Organism subdivision Anatomical system
CARO is a template for other anatomy
ontologies CARO allows reasoning across different
levels of granularity
5
Aligning a species-specific AO with CARO
CARO
zebrafish AO
is_a
Species-specific subtypes of CARO types
6
Mutant Gene Mutant or missing
ProteinMutant Phenotype (disease)
Linking animal models and human disease using
ontologies for phenotype annotation
Humans
Animal disease models
Mutant Gene Mutant or missing
ProteinMutant Phenotype (disease model)
7
Mutant Gene Mutant or missing
ProteinMutant Phenotype (disease)
Sequence analysis (BLAST) can connect animal
genes to human genes
Humans
Animal disease models
Mutant Gene Mutant or missing
ProteinMutant Phenotype (disease model)
8
Mutant Gene Mutant or missing
ProteinMutant Phenotype (disease)
Shared ontologies and syntax can connect mutant
phenotypes to candidate human disease genes
Humans
Animal disease models
Mutant Gene Mutant or missing
ProteinMutant Phenotype (disease model)
9
Annotation of eya phenotype using ontologies
zebrafish
fruitfly
human
entity
quality

Phenotype

eye
small

EQ

But these eyes are all different- does making
this comparison require homology assertion?
10
Queries for genes in homologous structures
chick
mouse
Niswander, 2003
Development of anatomical homologs may share
conserved genetic mechanisms
11
Queries for genes in similar structures

• Genetic mechanisms may be reused in similar
  structures
• Structures may be homologous in ways that are
  yet undetermined

Distal-less (Dll) expression
mouse limb
sea urchin tube feet
Panganiban et al., PNAS, 1997
polychaete parapodia
ascidian ampulla
12
Queries for genes in analogous structures

• Genetic mechanisms may be reused for similar
  purposes in analogous structures
• Structures may be homologous in ways that are
  yet undetermined

Vertebrate chambered heart
Process Conserved
genes Specification tinman/nkx2.5, wnts A-P
patterning Hox genes, RA Morphogenesis
Seven-up/Couptf-II
Arthropod dorsal vessel
Xavier-Neto et al., Cell Mol Life Sci, 2007
13
Simultaneous query for homologous, analogous, and
structurally similar anatomical entities
UBERON is a grouping ontology inclusive of other
AOs
UBERON is highly experimental and was created
by Xref links between species specific AOs and
CARO Curated mappings Text-based matching
(Obol)
UBERONinner ear
FMA16581 MGI0000293
XAO0003064 ZFA0000565
14
Resources OBO http//www.obofoundry.org/ CARO
wiki http//www.bioontology.org/wiki/index.php/CAR
OMain_Page Open Biological Database
(OBD) http//www.berkeleybop.org/obd/ Relations
wiki http//www.bioontology.org/wiki/index.php/RO
Main_Page Anatomy listserve https//lists.sourcef
orge.net/lists/listinfo/obo-anatomy FMA http//si
g.biostr.washington.edu/projects/fm/index.html
15
Homology example limb evolution
homologous_to
NOT homologous_to
descends_from