Download - Drysdale Pheno CSH
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7/29/2019 Drysdale Pheno CSH
1/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
The FlyBase Consortium:
Harvard University
University of Bloomington-Indiana
University of California-BerkeleyCambridge University
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7/29/2019 Drysdale Pheno CSH
2/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
FlyBase includes78,804 named alleles of19,053 Drosophilid genes
CLASSICAL ALLELES61,286
e.g. styS73 (EMS)
GENETICALLY ENGINEERED ALLELES17,518
e.g. styScer\UAS.cHa
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7/29/2019 Drysdale Pheno CSH
3/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Core vocabularies:
Phenotypic class (fbcv.obo)Anatomy (fly_anatomy.obo, GO)
Phenotypes are associated withalleles using
controlled vocabularies
in conjunction withcontrolled syntax
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7/29/2019 Drysdale Pheno CSH
4/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
The FlyBase record for styD5
(FBal0086316)includes:
Phenotypic class: neuroanatomy defective | recessivePhenotype manifest in: chordotonal organPhenotype manifest in: midline glial cell
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7/29/2019 Drysdale Pheno CSH
5/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Casci et al., 1999 used double mutant analysis to place styin the EGF receptor signaling pathway(GO:0007173).
Genetic interactionsfor 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 }
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7/29/2019 Drysdale Pheno CSH
6/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Single mutant phenotype statements:
Phenotypic class: 86,153Anatomy: 81,438
Total phenotypic data linesincluding free text: 397,821
Numbers
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7/29/2019 Drysdale Pheno CSH
7/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Genetic interaction statements:
Phenotypic class: 35,825
Anatomy: 39,686
Total multiple mutant phenotype linesincluding free text: 131,208
more
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7/29/2019 Drysdale Pheno CSH
8/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
ObservableAnatomiesGO Process
FunctionCell component
Cell TypeChemical metaboliteBehaviorTemporal/developmental/life
cycle
AttributeValue
The Phenotype Ontology idea so far:
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7/29/2019 Drysdale Pheno CSH
9/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
The Experiment:
9) Now each MOD should try toannotate 50 objects using PATO,and swop those around .
..Everyone do 50 units includeaspects of assay, etc/
Judy BlakeMay 2003 meetings Mins.
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7/29/2019 Drysdale Pheno CSH
10/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
The Questions:
1: Can the Phenotype Ontology represent all thecontrolled data thatFlyBase allele records include?
2: Can the Phenotype Ontology reduce the amountof free text information in FlyBase allele records?
3: Is the proposed system efficient enough forcurators for production database use?
4: Is the end product of this type of curationuseful to biologists?
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7/29/2019 Drysdale Pheno CSH
11/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
The Methods:
1. Identify candidate data-rich allelesselect annotation from one reference
2. Re-annotate with Phenotype Ontology System
3. Identifya. Structural problems?b. Vocabulary problems?c. Practical problems?
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7/29/2019 Drysdale Pheno CSH
12/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
asl1
FBal0030521
currently includes the followin g da ta, att ributed to:FBrf0104411 == Bonac corsi 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 | recessivePhenotyp e man ifest in : Nebenkern derivativePhenotyp e man ifest in : onion stage spermat id
Phenotyp e man ifest in : onion stage spermat id &nucleusPhenotyp e manifest in : (with asl2) spermatocyte & asterPhenotyp e manifest in : (with asl3) spermatocyte & asterPhenotyp e manifest in : first meiotic metapha se | mal ePhenotyp e man ifest in : first meiotic anaphas e | maleas l2/ as l1and asl3/ as l1 anima ls are viable .Onion stage spermat ids from homoz ygous males hav e
nuclei an d neben kern of var ious sizes.Homoz ygous, asl2/ as l1 and asl 3/as l1 sperm atoc ytes arecompletely devoid of asters. Homozygousspermatocytes hav e morpho logically norma lcentriole s. However, centr io le separa tion is abnormal;some nebenkern are associated with two centriolesinstead of one as in wild -type. Prom etaphas e I,metap hase I and early anap hase I appear to last longerin homozygous testes than in wild-type."
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7/29/2019 Drysdale Pheno CSH
13/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
asl
FBal0030521
Using Observable + attribute + value + qualifier+pm ontolog y term:
Phenotype: (w ith asl
2
) ad ult | viability | viable | re cess ive
Phenotype: (w ith asl3 ) ad ult | viability | vi able | recessive
Phenotype: adu lt | femal e_fertility | female_sterile | re cessiveORPhenoty pe: re pro du ct ion | fema le_fertility | f emale_sterile | re cessive
Phenotype: adu lt |m ale_fertility | m ale_sterile | recessive
ORPhenotype: re prod uct ion | mal e_fertility | ma le_sterile | re cessive
Phenoty pe: on ion stage spermatid & Nebe nkern | size | value\ :vari able??? | re cessive
Phenotype: onion stage sperm atid & nu cleus | size | value\:v ariable??? | recessive
Phenotype: (w ith asl2) spermatocyte & aster | qu antitative | absent | re cessive
Phenotype: (w ith asl3) spermatocyte & aster | qu antitative | absent | re cessive
Phenotype: cen triole & spermat ocyte | qualitative | norma l | re cessive
Phenoty pe: centrosome separa tion | p ro cess | value\ :abnorma l??? | re cessive
Phenotype: meiotic metaphas e I | re lative_speed | slow | re cessive
Phenotype: meiotic anap hase I | re lative_speed | slow | re cessive
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7/29/2019 Drysdale Pheno CSH
14/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
How much can we pack into one statement?
cac1 currently hasGenetic 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.
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7/29/2019 Drysdale Pheno CSH
15/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 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
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7/29/2019 Drysdale Pheno CSH
16/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Tricky to express
Free text things:asl1some nebenkern are associated with two centriolesinstead of one as in wild-typeabnormal relationship between two observables
Bsb2The laterals split near the distal tip as they elongateand at later stages they appear to be split over moreof their lengthobservables showing progressive defect
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7/29/2019 Drysdale Pheno CSH
17/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Caa1DAR66
A few homozygotes exhibit neurons in the longitudinaltracts that appear to stall at some of the commissures,forming nodular growthsbehaviour of one observable in relation to another
forming nodular growth?
egh27
Follicle cells at the posterior of egg chamber becomemesenchymal-liketransformation of one observable to another
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7/29/2019 Drysdale Pheno CSH
18/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Equivalent alternatives:
motor_neuron ; CL:0000100
motor 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
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7/29/2019 Drysdale Pheno CSH
19/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 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 | abnormalbut combined (better)Phenotype:morphogenesis of embryonic epithelium & embryonic head epidermis |process | abnormal
issue - attribute meaningful for one but not other observable - different kind of &
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7/29/2019 Drysdale Pheno CSH
20/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
Curation issues:
1: Need toolsbrowser where only relevant valuesfor specific attribute are presented
statement builder to assemble compoundphenotype terms sequentially from vocabs.
2: Redundancy solver - would certain combinations
be disallowed in statement builder?
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7/29/2019 Drysdale Pheno CSH
21/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005
The Answers:
1: Can the Phenotype Ontology represent all the
controlled data thatFlyBase allele records include?- potentially yes2: Can the Phenotype Ontology reduce the amountof free text information in FlyBase allele records?
-yes, but probably not eliminate it
3: Is the proposed system efficient enough forcurators for production database use?- no
4: Is the end product of this type of curationuseful to biologists?
- in searches yes though redundancy needs resolution,- for browsing? have found users to be tolerant
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7/29/2019 Drysdale Pheno CSH
22/22
Phenotype Ontology Meeting
Cold Spring HarborNovember 19-20th, 2005