Upload
roy-barton
View
215
Download
1
Embed Size (px)
Citation preview
Phenotype Ontology MeetingCold Spring Harbor
November 19-20th, 2005
The FlyBase Consortium:Harvard University
University of Bloomington-Indiana
University of California-Berkeley
Cambridge University
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
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
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
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 }
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 …
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 …
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:
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.
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?
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?
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."
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
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.
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
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
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
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
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 &
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?
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
Phenotype Ontology MeetingCold Spring Harbor
November 19-20th, 2005