11 Feb 2011, Science, Cover

12 Feb 2011 Science

Deluge of genomic data but it’s

computable...

Sea of phenomic data... not yet

computable

Translation?

photo J. Lundberg, ANSP 2002Pimelodus maculatus

Genes are conserved across divergent phenotypes

Courtesy of Kevin HelenurmUsed with permission from Micromundi: http://remf.dartmouth.edu/images/MicromondiImages/16chrysomelidae220.tif

Fig. 1, Washington et al., 2010

Translational medicine

Translation from model organisms to humans

Phenotype ontologies enable

discoveryEvolutionary phenotypes

from species

Gene phenotypes

from mutants

Phenotype extracted from literature

Phenotype annotation of gene

wild type

Zebrafish

GeneEntity

Quality

fam32al

Head Small size

Eye Small size

Ventral mandible Thick

Heart Edematous

Quality Ontology

(1,075 terms)

Gene Ontology

Zebrafish Anatomy Ontology

(2196 terms; 310 skeletal)

Quality Ontology

(1,323 terms) mutant

http://zfin.org/cgi-bin/webdriver?MIval=aa-fxfigureview.apg&OID=ZDB-FIG-070117-784

Phenotype annotation of taxon

species 1

TaxonEntity

Quality

species 1Head cylindrical

Adipose fin absent

species 2Head flat

Adipose fin present

Quality Ontology

(1,323 terms)

Teleost Taxonomy Ontology

(38,590 terms;59,664 synonyms)

Teleost Anatomy Ontology

(3,037 terms; 618 skeletal)

species 1

species 2

Brachyplatystoma capapretum

round thatinheres_in some

ethmoid cartilage

exhibits some

tfap2ats213/ts213split that

inheres_in someethmoid cartilage

influences some

round

split

ethmoid cartilageBrachyplatystom

a

tfap2a

is_a

variant_of inheres_

in

inheres_in

is_a

is_a

shape

chondrocranium cartilage

olfactory region

Pimelodidae

sequence-specific DNA binding

transcription factor activity

is_a

has_function is_a part_of

is_ais_a

Reasoning across logical relationships

500,000 testable hypotheses...

image:http://www.ustacrosport.com/buried-treasure

kb.phenoscape.org

Phenoscape Knowledgebase

501,862 taxon phenotypes

21,829 gene phenotypes for

3,893 genes

kb.phenoscape.org

Interativeuser

testing ofinterface

Anguilliforms,some catfish, e.g., Sisor rabdophorus, Chaca chaca

Harris et al., 2008

Gill rakers, absent

eda, edar,

taxa:

genes:

Are gill rakers absent in eels because of

changes in regulation of the eda pathway?

(2)(195)

Minytrema,Mullidae,Wolf eels

Chitramuthu et al., 2010

Smith, 1992

Lateral line, incomplete or absent

erbb3b, eya1,

pcsk5a, rog,

sox10, unm_m58

3

taxa: genes:

Is the reduced lateral line in Minytrema the

result of pcsk5a mutation?

(6)(102)

Mola,Gymnotiformes

Jiang et al., 2009

Britz & Johnson, 2005

Caudal fin, absent

smc3,

tll1,yap1

taxa:

genes:

Did Mola lose its caudal fin because of changes in regulation

of yap1?

(25) (3)

Tetraodontidae, Chanos, Gyrinocheilus,Liparidaesome Characiformes, etc.

Ceratobranchial 5 teeth, absent

eda, edar,

taxa: gen

es:Harris et al., 2008

http://www.brettb.com/images/AlgaeLoach2.jpg

Is loss of teeth in Gyrinocheilus related

to changes in regulation of eda?

(2)(30)

Gymnotiformessome silurids

Li et al., 2007Fink & Fink, 1981

Dorsal fin, absent

hoxa13a,

tfap2a

taxa:

genes:

Median finfold

Is the loss of a dorsal fin in South

American knifefishes connected to tfap2a?

(2)(58)

develops_from

Global view of skeletal data

Image from Sabaj-Perez

Skeletal variation across taxa and regions

viewed, summarized, synthesized, at a scale not possible otherwise.

Summary1.Genes mapped to taxa via phenotype

• Candidate genes • Candidate taxa

2.Powerful approach for data synthesis and discovery

3.Makes data accessible for broad group of researchers and creates opportunities for new and synthetic research

4.Future: ‘phenoblast’ search; vertebrates; homology