Phenoscape: Connectin g evolutionary phenotypes to genes Paula Mabee Hilmar Lapp, Todd Vision, Monte...
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Transcript of Phenoscape: Connectin g evolutionary phenotypes to genes Paula Mabee Hilmar Lapp, Todd Vision, Monte...
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Phenoscape: Connecting evolutionary
phenotypes to genes
Paula MabeeHilmar Lapp, Todd Vision, Monte
WesterfieldJim Balhoff, Wasila Dahdul, Peter
Midford
kb.phenoscape.org
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Difficult to synthesize morphology across
studies
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Difficult to relate to genetics & development
Cyprinus carpioCyprinus carpio
Pangio anguillarisPangio anguillaris
Nemacheilus fasciatusNemacheilus fasciatus
Catostomus commersoniCatostomus commersoni
Gyrinocheilus aymonieriGyrinocheilus aymonieri
Phenacogrammus interruptusPhenacogrammus interruptus
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have their basis in changes in genetic control over development
Phenotypic differencesPhenotypic differences
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Development understood from study of model organisms
Chen & Mayden, 2010
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Zebrafish
ntla
•Model for vertebrate development
•Mutagenesis/gene knock-down
•Mutant phenotypes genes
•ZFIN resource
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Problem:
photo J. Lundberg, ANSP 2002Pimelodus maculatus
•Species phenotypes genes at evolutionary scale
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slc24a5 involved in pigmentation similarity between fish and humans (Lamason et al., 2005)
Zebrafish -- HumanConservation of gene sequence &
function and phenotype
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Fig. 1, Washington et al., 2010
Translational medicine
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Ameiurus nebulosus
http://tolweb.org/Trogloglanis/69910
Fig. 1, Washington et al., 2010
Catfish
Trogloglanispattersoni
gene?EQ: eye absent
Translational biodiversity?
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Phenoscapekb.phenoscape.org
• 2007
•Goal: To prototype a curated, ontology-based evolutionary phenotype database that maps to genetic databases
•Devo-evo synthesis; candidate gene discovery
• Enable data-mining and discovery for broad scale evolutionary patterns
25 July 2009; ToL web
Ostariophysan fishes
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User needs drove KB development:
•Search for candidate genes underlying evolutionary morphology
•Search for taxa with particular morphologies
•Aggregate morphological data across studies
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Requirements (generic):
1.Ontologies
2.Curation
3.Database
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1. Ontology: terms and relationships
is_apart_of
is_a
develops_from
part_ofreplacemenreplacemen
t bonet bone
basihyal basihyal bonebone
ventral ventral hyoid archhyoid arch
basihyal basihyal cartilagecartilage
pharyngeal pharyngeal arch arch
cartilagecartilage
is_abasihyal basihyal elementelement
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Teleost Anatomy Ontology
2010. Dahdul, W. M., J. G. Lundberg, P. E. Midford, J. P. Balhoff, H. Lapp, T. J. Vision, M. A. Haendel, M. Westerfield, and P. M. Mabee. The Teleost Anatomy Ontology: Anatomical representation for the genomics age.
Systematic Biology (Cover art: Kyle Luckenbill)
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Ontologies used by Phenoscape
Zebrafish Anatomy Zebrafish Anatomy OntologyOntology(2196 terms; 310 skeletal)(2196 terms; 310 skeletal)
Zebrafish Anatomy Zebrafish Anatomy OntologyOntology(2196 terms; 310 skeletal)(2196 terms; 310 skeletal)
Teleost Teleost Taxonomy Taxonomy OntologyOntology
(36,060 terms;(36,060 terms;38,000 synonyms)38,000 synonyms)
Teleost Teleost Taxonomy Taxonomy OntologyOntology
(36,060 terms;(36,060 terms;38,000 synonyms)38,000 synonyms)
Taxonomic Taxonomic Rank Rank
OntologyOntology(8->31 terms)(8->31 terms)
Taxonomic Taxonomic Rank Rank
OntologyOntology(8->31 terms)(8->31 terms)
Teleost Anatomy Teleost Anatomy OntologyOntology
(2371 terms; 618 skeletal)(2371 terms; 618 skeletal)
Teleost Anatomy Teleost Anatomy OntologyOntology
(2371 terms; 618 skeletal)(2371 terms; 618 skeletal)
Phenotype and Phenotype and Trait Ontology Trait Ontology
(PATO)(PATO)(1,075 terms)(1,075 terms)
Spatial OntologySpatial Ontology(106 terms)(106 terms)
6 Jan 2009
EvidenceEvidenceCodeCode
OntologyOntology
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•Curated 4,732 characters in 2,474 species from 52 papers
•501,862 taxon phenotype annotations
•From ZFIN: 21,829 phenotype annotations about 3,893 genes
•Curated 4,732 characters in 2,474 species from 52 papers
•501,862 taxon phenotype annotations
•From ZFIN: 21,829 phenotype annotations about 3,893 genes
2. CurationDahdul et al., 2010 PLoS ONE
2. Students: Manual entry of
free text character descriptions,
matrix, taxon list, specimens and
museum numbers using Phenex
2. Students: Manual entry of
free text character descriptions,
matrix, taxon list, specimens and
museum numbers using Phenex
3. Character annotation by
experts: Entry of phenotypes using
Phenex
3. Character annotation by
experts: Entry of phenotypes using
Phenex
Curators:Wasila DahdulMiles CoburnJeff EngemenTerry GrandeEric HiltonJohn LundbergPaula MabeeRichard MaydenMark Sabaj Pérez
~ 5 person years~ 5 person years
1. Students: gather publications (scan
hard copies, produce OCR PDFs)
1. Students: gather publications (scan
hard copies, produce OCR PDFs)
4. Phenoscape Knowledgebase: OBD,
data services, web application
4. Phenoscape Knowledgebase: OBD,
data services, web application
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5K Karacter ChallengeOntology boot camp,
NESCent 2005Phenoscape Data Roundup
photo: NESCent
photo: Monte Westerfield
Buffalo Roundup, SD
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Entity-Quality Model for Taxon Phenotypes
ethmoid cartilageethmoid cartilage
ethmoid plate formethmoid plate form
Entity (TAO)
roundedrounded
Character
roundround
Quality (PATO)
State}Phenotype
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Taxon phenotype annotations
round that
inheres_in some
ethmoid cartilage
round that
inheres_in some
ethmoid cartilage
exhibits some
Taxon ontology term
Anatomy ontology term
Phenotypic Quality ontology term
Links a quality to the entity that is its
bearer
Brachyplatystoma capapretum
Brachyplatystoma capapretum
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split that
inheres_in some
ethmoid cartilage
split that
inheres_in some
ethmoid cartilage
influences some
Gene phenotype annotations
Import from ZFIN data in EQ format
tfap2ats213/ts213
tfap2ats213/ts213
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Brachyplatystoma capapretum
Brachyplatystoma capapretum
round that
inheres_in some
ethmoid cartilage
round that
inheres_in some
ethmoid cartilage
exhibits some
tfap2ats213/ts213
tfap2ats213/ts213
split that
inheres_in some
ethmoid cartilage
split that
inheres_in some
ethmoid cartilage
influences some
roundround
splitsplit
ethmoid cartilage
ethmoid cartilage
Brachyplatystoma
Brachyplatystoma
tfap2atfap2a
is_a
variant_of inheres_
in
inheres_in
is_a
is_a
shapeshape
chondrocranium cartilage
chondrocranium cartilage
olfactory region
olfactory region
PimelodidaePimelodidae
sequence-specific DNA binding
transcription factor activity
sequence-specific DNA binding
transcription factor activity
is_a
has_function is_a part_of
is_ais_a
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Knowledgebase architecture
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Phenoscape Knowledgebase
501,862 taxon phenotypes
21,829 gene phenotypes for
3,893 genes
kb.phenoscape.org
Interativeuser
testing ofinterface
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KB inferred candidate genes
Phenotypic profile for Siluriformes
includes:Scales absent; Basihyal absent
Phenotypic profile for Siluriformes
includes:Scales absent; Basihyal absent
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30% <1%
position
composition
25% 20% 15% 10%
count
shape structuresize
PATO qualities used in phenotypes
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Siluriform synapomorphies:
Ictalurus punctatus
Copyright © Jean Ricardo Simões Vitule, All Rights Reserved
Scales absent Basihyal absent
Ictalurus punctatus
Photo: Richard Edmunds
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Zebrafish mutant phenotypes
Harris et al., 2007
eda: scale loss brpf1: basihyal loss
Laue et al., 2008
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In silico prediction of candidate genes
Ictalurus punctatus
Copyright © Jean Ricardo Simões Vitule, All Rights Reserved
Scales absent: eda? Basihyal absent: brpf1?
Ictalurus punctatus
Photo: Richard Edmunds
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Wet lab test (Richard Edmunds)
Lack of eda expression in the epidermis supports Phenoscape KB
hypothesis
Ictalurus punctatus
eda
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Wet lab test (Richard Edmunds)Ictalurus punctatus
78 hpf 86 hpfLack of brpf1 expression in the basihyal supports Phenoscape KB
hypothesis
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E.g., distribution of all characters across
anatomical systems in taxa
25 July 2008
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E.g., distribution of skeletal characters in broad regions
across taxa
Image from Sabaj-Perez
25 July 2008
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Summary•Powerful queries not previously
possible for evolutionary phenotype data
•Meaningful integration with model organism phenotypic and genetic data
•Makes data accessible for broad group of researchers and creates opportunities for new and synthetic research
Semantic framework and reasoning tools provide:
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Phenoscape as a resource
•Ontologies (anatomy, quality, taxon) + EQ data for any taxon
•Reasoning across EQ data types, uniting multiple studies, genes, etc.
•Your data?
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AcknowledgmentsPhenoscape Personnel & PIs:P. Mabee,M. Westerfield, T. Vision,H. Lapp,C. Kothari,W. Dahdul,P. Midford,R. EdmundsPhenoscape curators & workshop participants
Berkeley Bioinformatics & Ontologies Project (BBOP):C.Mungall, S.LewisNational Evolutionary Synthesis Center (NESCent)NSF (DBI 0641025)