the flybase consortium: harvard university university of bloomington-indiana

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Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 The FlyBase Consortium: Harvard University University of Bloomington-Indiana University of California-Berkeley Cambridge University

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The FlyBase Consortium: Harvard University University of Bloomington-Indiana University of California-Berkeley Cambridge University. FlyBase includes 78,804 named alleles of 19,053 Drosophilid genes C LASSICAL A LLELES 61,286 e.g. sty S73 (EMS) G ENETICALLY E NGINEERED A LLELES - PowerPoint PPT Presentation

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Page 1: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

The FlyBase Consortium:Harvard University

University of Bloomington-Indiana

University of California-Berkeley

Cambridge University

Page 2: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

FlyBase includes 78,804 named alleles of 19,053 Drosophilid genes

CLASSICAL ALLELES61,286

e.g. styS73 (EMS)

GENETICALLY ENGINEERED ALLELES17,518

e.g. styScer\UAS.cHa

Page 3: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Core vocabularies:

Phenotypic class (fbcv.obo)

Anatomy (fly_anatomy.obo, GO)

Phenotypes are associated with alleles using

controlled vocabularies in conjunction with controlled syntax

Page 4: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

The FlyBase record for sty5

(FBal0086316) includes:

Phenotypic class: neuroanatomy defective | recessivePhenotype manifest in: chordotonal organPhenotype manifest in: midline glial cell

Page 5: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Casci et al., 1999 used double mutant analysis to place sty in the EGF receptor signaling pathway (GO:0007173).

Genetic interactions…for example

Genetic interaction: suppressor | dominant, visible { argosGMR.PC }Genetic interaction: suppressor | dominant, eye { argosGMR.PC }

Genetic interaction: enhancer | dominant, visible { Shs.sev }Genetic interaction: enhancer | dominant, eye { Shs.sev }

Page 6: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Single mutant phenotype statements:

Phenotypic class: 86,153Anatomy: 81,438

Total phenotypic data lines including free text: 397,821

Numbers …

Page 7: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Genetic interaction statements:

Phenotypic class: 35,825Anatomy: 39,686

Total multiple mutant phenotype lines including free text: 131,208

more …

Page 8: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

ObservableAnatomiesGO Process

FunctionCell component

Cell TypeChemical metaboliteBehaviorTemporal/developmental/life

cycleAttributeValue

The Phenotype Ontology idea so far:

Page 9: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

The Experiment:

“9) Now each MOD should try to annotate 50 objects using PATO, and swop those around …...Everyone do “50 units” … include aspects of assay, etc/”

Judy BlakeMay 2003 meeting’s Mins.

Page 10: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

The Questions:

1: Can the Phenotype Ontology represent all the controlled data that FlyBase allele records include?

2: Can the Phenotype Ontology reduce the amount of free text information in FlyBase allele records?

3: Is the proposed system efficient enough for curators for production database use?

4: Is the end product of this type of curation useful to biologists?

Page 11: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

The Methods:

1. Identify candidate data-rich alleles select annotation from one reference

2. Re-annotate with Phenotype Ontology System3. Identify a. Structural problems? b. Vocabulary problems? c. Practical problems?

Page 12: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

asl1

FBal0030521

currently includes the following data, attributed to:FBrf0104411 == Bonaccorsi et al., 1998, J. Cell Biol.142(3): 751--761

Phenotypic class: (with asl2) viablePhenotypic class: (with asl3) viablePhenotypic class: male sterile | recessivePhenotypic class: female sterile | recessivePhenotype manifest in: Nebenkern derivativePhenotype manifest in: onion stage spermatidPhenotype manifest in: onion stage spermatid &nucleusPhenotype manifest in: (with asl2) spermatocyte & asterPhenotype manifest in: (with asl3) spermatocyte & asterPhenotype manifest in: first meiotic metaphase | malePhenotype manifest in: first meiotic anaphase | male“asl2/ asl1and asl3/ asl1 animals are viable.Onion stage spermatids from homozygous males havenuclei and nebenkern of various sizes.Homozygous, asl2/ asl1 and asl3/asl1 spermatocytes arecompletely devoid of asters. Homozygousspermatocytes have morphologically normalcentrioles. However, centriole separation is abnormal;some nebenkern are associated with two centriolesinstead of one as in wild-type. Prometaphase I,metaphase I and early anaphase I appear to last longerin homozygous testes than in wild-type."

Page 13: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

asl1

FBal0030521

Using Observable + attribute + value + qualifier + pm ontology term:

Phenotype: (with asl2 ) adult | viability | viable | recessive

Phenotype: (with asl3 ) adult | viability | viable | recessive

Phenotype: adult | female_fertility | female_sterile | recessiveORPhenotype: reproduction | female_fertility | female_sterile | recessive

Phenotype: adult | male_fertility | male_sterile | recessiveORPhenotype: reproduction | male_fertility | male_sterile | recessive

Phenotype: onion stage spermatid & Nebenkern | size | value\ :variable??? | recessive

Phenotype: onion stage spermatid & nucleus | size | value\:v ariable??? | recessive

Phenotype: (with asl2) spermatocyte & aster | quantitative | absent | recessive

Phenotype: (with asl3) spermatocyte & aster | quantitative | absent | recessive

Phenotype: centriole & spermatocyte | qualitative | normal | recessive

Phenotype: centrosome separation | p rocess | value\ :abnormal??? | recessive

Phenotype: meiotic metaphase I | relative_speed | slow | recessive

Phenotype: meiotic anaphase I | relative_speed | slow | recessive

Page 14: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

How much can we pack into one statement?

cac1 currently hasGenetic interaction: song defective | recessive, enhanceable { mlenap-ts1 }

New system would beGenetic interaction: male courtship behavior (sensu Insecta)\, song production | process | abnormal | recessive, enhanceable { mlenap-ts1 }

Point - if values were linguistically distinct then no need to state ‘attribute’ instatement as attribute would be implicit from the attribute:value relationship.

Page 15: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Another example

Allele combinations:as in asl1:Phenotype manifest in: (with asl2) spermatocyte & aster

New system would bePhenotype: (with asl2) spermatocyte & aster | quantitative | absent

again - better were ‘quantitative’ attribute implicit and unstated

(with asl2) spermatocyte & aster | absent

Page 16: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Tricky to express …

Free text things:asl1

“some nebenkern are associated with two centrioles instead of one as in wild-type”abnormal relationship between two observables

Bsb2

“The laterals split near the distal tip as they elongate and at later stages they appear to be split over more of their length”observables showing progressive defect

Page 17: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Ca1DAR66

“A few homozygotes exhibit neurons in the longitudinal tracts that appear to stall at some of the commissures, forming nodular growths”behaviour of one observable in relation to another‘forming nodular growth’?

egh27

“Follicle cells at the posterior of egg chamber become mesenchymal-like”transformation of one observable to another

Page 18: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Equivalent alternatives:

motor_neuron ; CL:0000100motor neuron ; FBbt:00005123

cell ; GO:0005623cell_in_vivo ; CL:0000003

adult | male_fertility | male sterile | recessivereproduction | male_fertility | male sterile | recessive

real issue - if redundancy exists then utility of PO for providing comprehensive access to all phenotypes of same class is compromised

Page 19: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Structural issue:

Sense of compound observable/attribute combination:Observation: “phenotype is in dorsal epithelium that makes the embryonic head”

Phenotype: morphogenesis of embryonic epithelium | process | abnormal

Phenotype: embryonic head epidermis | dorsal | qualitative | abnormal

but combined (better)Phenotype: morphogenesis of embryonic epithelium & embryonic head epidermis | process | abnormal

issue - attribute meaningful for one but not other observable - different kind of &

Page 20: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

Curation issues:

1: Need tools browser where only relevant values for specific attribute are presented “statement builder” to assemble compound phenotype terms sequentially from vocabs.

2: Redundancy solver - would certain combinations be disallowed in statement builder?

Page 21: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005

The Answers:

1: Can the Phenotype Ontology represent all the controlled data that FlyBase allele records include? - potentially yes2: Can the Phenotype Ontology reduce the amount of free text information in FlyBase allele records? -yes, but probably not eliminate it3: Is the proposed system efficient enough for curators for production database use? - no4: Is the end product of this type of curation useful to biologists? - in searches yes though redundancy needs resolution,- for browsing? have found users to be tolerant

Page 22: The FlyBase Consortium: Harvard University University of Bloomington-Indiana

Phenotype Ontology MeetingCold Spring Harbor

November 19-20th, 2005