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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

78,804 named alleles of 19,053 Drosophilid genes CLASSICAL ALLELES 61,286


e.g. styS73 (EMS)

FlyBase includes

GENETICALLY ENGINEERED ALLELES 17,518


e.g. styScer\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 styD5 (FBal0086316) 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

Genetic interactionsfor example


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

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

Numbers
Single mutant phenotype statements:
Phenotypic class: 86,153 Anatomy: 81,438
Total phenotypic data lines including free text: 397,821

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

more
Genetic interaction statements:
Phenotypic class: 35,825 Anatomy: 39,686
Total multiple mutant phenotype lines including free text: 131,208

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

The Phenotype Ontology idea so far:


Observable Anatomies GO Process Function Cell component Cell Type Chemical metabolite Behavior Temporal/developmental/life cycle Attribute Value

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 meetings 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

asl 1 FBal0030521
current ly inclu d es th e follow in g da ta, att ribu ted to: FBrf0104411 == Bonac corsi et al., 1998, J. Cell Biol. 142(3): 751--761 Phenotypic class: (with asl2) viable Phenotypic class: (with asl3) viable Phenotypic class: male ster ile | recessive Phenotypic class: femal e sterile | recessive Phenotype manifest in : Ne ben ker n d er ivat ive Phenotype manifest in : onion stag e sper mat id Phenotype manifest in : onion stag e sper mat id & nuc le us Phenotype manifest in : (with asl2) sper ma tocyte & aster Phenotype manifest in : (with asl3) sper ma tocyte & aster Phenotype manifest in : first meiotic m etapha se | mal e Phenotype manifest in : first meiotic anaphas e | m ale as l2/ asl1an d asl3/ asl1 anima ls ar e viab le . On ion stage sper mat ids from homoz yg ous mal es hav e nuc le i an d nebe nkern of var iou s sizes. H omoz yg ou s, asl2/ asl1 and asl 3/as l1 sperm atoc ytes are com pletely de void of aster s. Homoz yg ous sper mat ocytes hav e m orpho logicall y no rma l centriole s. How eve r, cen triole separa tion is abno rma l; some nebe nkern are associat ed wit h tw o cent rioles instead of on e as in wild -typ e. Prom et aphas e I, Ontology Meeting m etap h ase I and Phenotype ear Cold ly anap hase I ap pear to la st lon ger Spring Harbor in homoz yg ous testes than in wild -typ e." November 19-20th, 2005

asl 1 FBa l0030521 Usin g Obser vable + attribu te + value + q ualifier + p m o ntolog y ter m : Ph enotyp e: (w ith asl2 ) ad u lt | v iab ility | v iab le | re cessive Ph enotyp e: (w ith asl3 ) ad u lt | v iability | vi ab le | recessive Ph enotyp e: ad u lt | fe mal e_fer tility | fem ale_ster ile | re cessive OR Ph enotyp e: re p ro d u ct ion | fema le_ fer tility | f em ale_ster ile | re cessive Ph enotyp e: ad u lt | m ale_fer tility | m ale_ste rile | rece ssive OR Ph enotyp e: re p ro d u ct ion | mal e_fer tility | ma le_ster ile | re cessive Ph enotyp e: o nion stage sper m atid & Nebe nk ern | size | v alu e\ :v ari able??? | re cessiv e Ph enotyp e: o nion stage sper m atid & nu cleu s | size | v alu e\:v ar iable??? | recessive Ph enotyp e: (w ith asl2) sper m atocyte & as ter | q u antitative | ab sen t | re cessive Ph enotyp e: (w ith asl3) sper m atocyte & as ter | q u antitative | ab sen t | re cessive Ph enotyp e: cen triole & sp er mat ocyte | q ua litative | no rma l | re cessive Ph enotyp e: cen tro som e sep ara tion | p ro cess | v alu e\ :ab norm al??? | re cessive Ph enotyp e: meiotic m etap has e I | re lative_sp eed | slow | re cessive
Cold Harboreed | slow | re cessive Ph enotyp e: meiotic anap hase I | Spring re lative_sp Phenotype Ontology Meeting

November 19-20th, 2005

How much can we pack into one statement?


cac1 currently has Genetic interaction: song defective | recessive, enhanceable { mlenap-ts1 } New system would be Genetic 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 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 asl1: Phenotype manifest in: (with asl2) spermatocyte & aster New system would be Phenotype: (with asl2) spermatocyte & aster | quantitative | absent
again - better were quantitative attribute implicit and unstated

(with asl2) spermatocyte & aster | absent

Phenotype Ontology Meeting Cold 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

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

Caa1DAR66 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

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

Equivalent alternatives:
motor_neuron ; CL:0000100 motor neuron ; FBbt:00005123

cell ; GO:0005623 cell_in_vivo ; CL:0000003


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

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

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