drysdale pheno csh

7/29/2019 Drysdale Pheno CSH

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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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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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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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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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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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Single mutant phenotype statements:

Phenotypic class: 86,153Anatomy: 81,438

Total phenotypic data linesincluding free text: 397,821

Numbers


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Genetic interaction statements:

Phenotypic class: 35,825

Anatomy: 39,686

Total multiple mutant phenotype linesincluding free text: 131,208

more


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ObservableAnatomiesGO Process

FunctionCell component

Cell TypeChemical metaboliteBehaviorTemporal/developmental/life

cycle

AttributeValue

The Phenotype Ontology idea so far:


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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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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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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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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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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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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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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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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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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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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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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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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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