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

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 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 17,518 e.g. sty Scer\UAS.cHa

Phenotype Ontology Meeting Cold 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

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 The FlyBase record for sty  5 (FBal ) includes: Phenotypic class: neuroanatomy defective | recessive Phenotype manifest in: chordotonal organ Phenotype manifest in: midline glial cell

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Casci et al., 1999 used double mutant analysis to place sty in the EGF receptor signaling pathway (GO: ). Genetic interactions…for example Genetic interaction: suppressor | dominant, visible { argos GMR.PC } Genetic interaction: suppressor | dominant, eye { argos GMR.PC } Genetic interaction: enhancer | dominant, visible { S hs.sev } Genetic interaction: enhancer | dominant, eye { S hs.sev }

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Single mutant phenotype statements: Phenotypic class: 86,153 Anatomy: 81,438 Total phenotypic data lines including free text: 397,821 Numbers …

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Genetic interaction statements: Phenotypic class: 35,825 Anatomy: 39,686 Total multiple mutant phenotype lines including free text: 131,208 more …

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Observable Anatomies GO Process Function Cell component Cell Type Chemical metabolite Behavior Temporal/developmental/life cycle Attribute Value The Phenotype Ontology idea so far:

Phenotype Ontology Meeting Cold 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 Blake May 2003 meeting’s Mins.

Phenotype Ontology Meeting Cold 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?

Phenotype Ontology Meeting Cold 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 System 3.Identify a. Structural problems? b. Vocabulary problems? c. Practical problems?

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 How much can we pack into one statement? cac 1 currently has Genetic interaction: song defective | recessive, enhanceable { mle nap-ts1 } New system would be Genetic interaction: male courtship behavior (sensu Insecta)\, song production | process | abnormal | recessive, enhanceable { mle nap-ts1 } Point - if values were linguistically distinct then no need to state ‘attribute’ in statement as attribute would be implicit from the attribute:value relationship.

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Another example Allele combinations: as in asl 1 : Phenotype manifest in: (with asl 2 ) spermatocyte & aster New system would be Phenotype: (with asl 2 ) spermatocyte & aster | quantitative | absent again - better were ‘quantitative’ attribute implicit and unstated (with asl 2 ) spermatocyte & aster | absent

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Tricky to express … Free text things: asl 1 “some nebenkern are associated with two centrioles instead of one as in wild-type” abnormal relationship between two observables Bsb 2 “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

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Ca  1D AR66 “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’? egh 27 “Follicle cells at the posterior of egg chamber become mesenchymal-like” transformation of one observable to another

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 Equivalent alternatives: motor_neuron ; CL: motor neuron ; FBbt: cell ; GO: cell_in_vivo ; CL: adult | male_fertility | male sterile | recessive reproduction | 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

Phenotype Ontology Meeting Cold 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 &

Phenotype Ontology Meeting Cold 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?

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005 The Answers: 1: Can the Phenotype Ontology represent all the controlled data that FlyBase allele records include? - potentially yes 2: Can the Phenotype Ontology reduce the amount of free text information in FlyBase allele records? -yes, but probably not eliminate it 3: Is the proposed system efficient enough for curators for production database use? - no 4: 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

Phenotype Ontology Meeting Cold Spring Harbor November 19-20th, 2005