Data integration challenge entry presentation for iEvoBio 2011.

1. Phenoscape
Knowledgebase
Jim Balhoff, Wasila Dahdul, Hilmar Lapp, Paula Mabee,
Peter Midford, Todd Vision, Monte Westerfield

2. Phenoscape
• Collaboration between P. Mabee (U. South Dakota), M.
Westerfield (ZFIN, U. Oregon), and T.Vision (NESCent,
UNC)
• Aim: foster semantic integration of phenotype data by
• Prototyping a database of curated, machine-interpretable
evolutionary phenotypes.
• Integrating these with mutant phenotypes from model
organisms.
• Providing reasoner-enabled semantic tools which facilitate
data-mining of phenotypic diversity and discovery of
candidate genes for evolutionary phenotype transitions.

3. Phenoscape Knowledgebase
• ~4 million asserted semantic links (+ 7 million inferred)
• 52 fish systematics publications
• 4700 morphological characters
• 11,000 states + ontological descriptions (EQ)
• 2500 referenced taxa
• ZFIN
• 3900 genes, 6800 genotypes
• 30000 experimental phenotype annotations
• 13 ontologies
• ~80,000 terms

4. Workflow for phenotype annotation
3. Character annotation
2. Students: by experts: Entry of
Manual entry of free text phenotypes using
character descriptions, Phenex
matrix, taxon list,
specimens and museum
numbers using Phenex
4. Phenoscape Knowledgebase:
OBD, data services, web
application
501,862
1. Students:
gather publications (scan phenotypes for
hard copies, produce
OCR PDFs) taxa
Dahdul et al., 2010 PLoS ONE Text

5. Knowledgebase architecture
Knowledgebase User Inteface External web sites
Web Application for Exploration & Mining and client
(Ruby on Rails, JavaScript) applications
Knowledgebase Data Services API (REST)
OBD Programming API
OBD Reasoner
(Java)
Teleost Taxonomy
Ontology (TTO)
Knowledgebase (OBD)
(PostgreSQL)
Phenotypic
Anatomy Quality Ontology
Ontologies (PATO)
(ZFA, TAO)
Genes & genotypes Homology assertions
Mutant EQ phenotypes Evolutionary EQ Phenotypes NeXML
OBO Library
from Zebrafish Model (through annotation)
Organism Database
Phenex Skeletal Character Data
(Evolutionary EQ (from phylogenetic
annotation) treatments in literature)

6. OBD: Ontology-Based Database
• Stores data and ontologies in combined
semantic model - triple based
• Reasoner executes inference rules as SQL
queries - results iteratively added to database
• Supports class expressions based on property
restrictions, intersections, unions; transitive
properties, property chains, and subsumption
• Provenance-tracking via reification

7. Reasoning across logical relationships
Brachyplatystoma exhibits some round that
capapretum inheres_in some
ethmoid cartilage
influences some split that
tfap2a ts213/ts213
inheres_in some
ethmoid cartilage

8. Reasoning across logical relationships
tfap2a
ethmoid
Brachyplatystoma cartilage
round
variant_of
is_a inheres_in
is_a
Brachyplatystoma exhibits some round that inheres_in split
capapretum inheres_in some
ethmoid cartilage
is_a
influences some split that
tfap2a ts213/ts213
inheres_in some
ethmoid cartilage

9. Reasoning across logical relationships
sequence-specific DNA olfactory
binding transcription
factor activity chondrocranium region
cartilage
Pimelodidae shape
has_function part_of
is_a
is_a
is_a is_a
tfap2a
ethmoid
Brachyplatystoma cartilage
round
variant_of
is_a inheres_in
is_a
Brachyplatystoma exhibits some round that inheres_in split
capapretum inheres_in some
ethmoid cartilage
is_a
influences some split that
tfap2a ts213/ts213
inheres_in some
ethmoid cartilage

10. Demo

11. Phenotype variation
in taxa (left) vs. zebrafish mutants (right)
cardiovascular
digestive
skeletal
is_a
is_a
is_a endocrine
sensory is_a
is_a
anatomical is_a
hematopoietic
respiratory is_a
system is_a
is_a immune
is_a
is_a
is_a is_a
liver and biliary
reproductive
renal musculature
nervous
>85% 20-30% 15-19% 10-14% 5-9% 1-4% <1%
Distributed across anatomical systems

12. Global view of skeletal data
4,-62+/0.123"
viewed, summarized,
synthesized, at a scale not
possible otherwise. =">03?:.97+9,"9@+9,"3A2,2?07"
;070.57:8+/0.123"
=">9+.2B"C73"
;5170</0.123"
=""4.97+-1"
489.9:+/0.123"
456.+7+/0.123"
*+,-.+/0.123" Image from Sabaj-Perez
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Skeletal variation across taxa and regions

13. Quantify phenotypic similarity
Similarity Taxon Candidate Gene Subsuming
Taxon
(IC) phenotype gene phenotype phenotype
13.43 Eels gill rakers, absent eda gill rakers, absent gill rakers count
lateral line,
12.85 Minytrema lateral line, absent pcsk5a lateral line, size
reduced
12.44 Siluriformes basihyal, absent brpf1 basihyal, absent basihyal, count
ceratobranchial 5 ceratobranchial
11.32 Gyrinocheilus eda tooth, count
teeth, absent teeth, absent
11.11 Siluriformes scales, absent eda scales, absent scales, count
dermatocranium,
9.91 Siluriformes opercle, shape edn1 maxilla, shape
shape
9.19 Mola caudal fin, absent yap1 median fin, absent median fin, count
9.19 Gonorynchiformes dorsal fin, absent tf1p2a median fin, absent median fin, count
5.17 Siluriformes eye, reduced pbx2 eye, small eye, size

14. Summary
Semantic framework and reasoning tools provide:
• Powerful queries not previously possible
for evolutionary phenotype data
• Meaningful integration with model
organism phenotypic and genetic data

15. Acknowledgments
Phenoscape Workshop Participants
National Science Foundation (BDI-0641025) & Contributors
! Arhat Abzhanov
National Evolutionary Synthesis Center !
!
Michael Ashburner
Judith Blake
! Stan Blum
! Quentin Cronk
Contributors to Teleost Ontologies Curators: ! Mário de Pinna
! Andy Deans
! Gloria Arratia Miles Coburn ! George Gkoutos
! Melissa Haendel
! Stan Blum ! Jeff Engemen ! Hopi Hoekstra
! Miles Coburn
! Kevin Conway ! Terry Grande ! Hans Hofmann
! Elizabeth Jockusch
! Wasila Dahdul ! Eric Hilton ! Elizabeth Kellogg
! Mário de Pinna
! Jeff Engemen ! John Lundberg ! Chuck Kimmel
! Suzanna Lewis
! Bill Eschmeyer ! Paula Mabee ! Anne Maglia
! Terry Grande
! Melissa Haendel ! Richard Mayden ! Austin Mast
! Brian Hall ! Chris Mungall
! Mark Sabaj ! Martin Ramirez
! Eric Hilton
! John Lundberg Sandrine Tercerie ! Sue Rhee
! Richard Mayden ! Martin Ringwald
! Mark Sabaj Pérez ! Nelson Rios
! Brian Sidlauskas ! Mark Sabaj Pérez
! Richard Vari ! Eric Segerdell
! Jacqueline Webb ! Brian Sidlauskas
! Edward Wiley ! Barry Smith
! David Stern
! Peter Vize
! Gunter Wagner
! Nicole Washington
! Edward Wiley