Difference between revisions of "Phenoscape Grant Renewal Workshop/Notes"

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** Can we retrieve the characters that are discordant?
** Can we retrieve the characters that are discordant?
* What question motivates character matrix?
* What question motivates character matrix?
== Developmental time and use case discussion
== Developmental time & use case discussion ==
== Wednesday morning ==
== Wednesday morning ==

Revision as of 17:09, 22 May 2009

Phenoscape II: Tuesday, April 28, 1:00-5:30

Participating: Phenoscape: Paula Mabee, Todd Vision, Monte Westerfield, Hilmar Lapp, Wasila Dahdul, Jim Balhoff, Cartik Kothari, Peter Midford, John Lundberg; Suzanna Lewis, Judy Blake, Peter Vize, Anne Maglia

  • Will be extending the taxonomic scope to extant and extinct vertebrates
    • Create an annotation database spanning the taxonomic scope and their anatomy ontologies
    • Three multi-species anatomy ontologies are being developed: teleosts, amphibians, mammalian anatomy
    • Tree mapping: show when an evolutionary phenotype first appeared
  • EQ support in all involved model organism databases
    • Structure of MP is not consistent with anatomy, or with PATO
    • Mapping from MP to EQ syntax is being worked on (George Gkoutos)
      • How is this supported in MGI?
        • Could spit back EQ, but could not allow users to search
    • MGI isn't in a position to use EQ internally, but for example Phenoscape II could provide an EQ-view on mouse phenotypes, using the decomposition of MP into anatomy (or entity) and quality term cross-product
    • Full EQ annotation for OMIM is being planned but not yet funded
    • MGI, Xenbase, and ZFIN all have links from their phenotype data to OMIM
  • Phenoscape II: Development of anatomy - new queries supported; would generate testable hypotheses; how exactly do those queries rely on developmental data?
    • Different approaches between MGI and ZFIN:
      • MGI uses complete anatomy at different developmental stages
      • ZFIN uses one anatomy ontology and adds start and end dates to indicate the developmental period during which it appears (adult structures don't have an end date)
      • Xenbase uses the ZFIN approach
    • Candidate genes for evolutionary change could be derived from anatomy-annotated gene expression studies during development; Where do mouse and Xenopus share gene sets in early development?
      • genes responsible for or associated with morphological changes during individual development could be candidates for evolutionary change
      • evolutionary phenotype changes could be used to query morphological changes during development
    • Can we enable queries to generate hypotheses based on ontogeny reflecting evolutionary history?
    • Powerful tool in interpreting microarray data downstream from node; know candidate genes without mutants using this approach
    • See phenotypic differences between 2 taxa – where do you see similar changes?
    • Cell types and associate with time and space – can reason from, neural crest, etc.
      • Evolutionary developmental data could come from medaka, stickleback
  • Sequence of steps:
    1. Ontology building
      • Adult phenotype annotations for mutants in Xenbase
      • Presently only 3 species for amphibians: Xenopus, Dermophis, Salamandria (integration beginning in July; phenotypes/mutants, adulta; L. Zimmerman (GB))
      • Development decoupling from anatomy ontology in mouse (as per above)
        • Requirements:
          • QC required – 1 person to find orphans and generate reports (80% complete); make decisions
          • 1st: alignment of MP and mouse anatomy, then QC of MP-EQ; use Mouse anatomy to initalize Paul’s ontology
          • 2nd: Mouse staging-> ZFIN + Xenbase style
          • Phenoscape II: Time required for above (1st and 2nd) is 1 person over 3 years
      • Expanding mammalian anatomy to include extinct species
          • Judy mentioned Fiona McCarthy (chick ontology? Judy will ask)
      • Anatomy for amniotes (the clade including mouse and dinosaurs), including extinct taxa (such as dinosaurs)
        • Scope of this could be overwhelming
        • Should be strongly driven (or staged) according to the character matrices to be annotated
        • Chicken anatomy could provide a starting point?
        • There is work on bird anatomy that uses a latin naming scheme
        • Work on any smaller-scope anatomy (or multi-species anatomy) ontology will contribute terms that apply more broadly
        • There may not be very many neomorphs between birds and mammals, though there are a few areas such as the digits in birds where the exact homology relationships aren't as clearly agreed upon.
        • set up ontology and extend to fossils that Paul knows best;
        • also need taxonomy onotlogy (from suprageneric filemaker database?)
    2. Mammalian phenotype decomposition
      • Need support for QC'ing the results of automated decomposition
      • Alignment of MP with mouse anatomy
    3. Annotation
      • Which published character matrices are there for dinosaurs?
  • Ontology mapping and alignment
    • Need to align teleost and amphibian anatomy to mouse.
    • Mouse and chicken need to be mapped to amniote anatomy. Mouse is a better start because there are genetic data.
  • Paul Sereno gave short presentation on reconciling character-derived trees and character definition and use between different matrices and trees that share taxa
    • TaxonSearch
    • Formalizing and generating grammar of character coding and character state definition
      • Phenoscape II grant activity could be to produce EQ primer
    • presented summaries of annotations, by region, by authors, by structure, by quality
    • Paul’s question: Why are 2 trees different? A: Particular characters and types of coding; If you are trying to develop a consensus tree – can see how authors’ differ
    • Analyzing character usage (shared, not shared, rejected) between trees that share taxa
    • Conflicting phylogenies for the same set of taxa often turn out to be based on character codings that are not consistent or not compatible
    • need to not only curate legacy data but be proactive in terms of syntax etc. of future data; use cases looking forward; morphology in crisis, wallowing in a sea of data
  • Re: direct submission --Monte: ZFIN has 6,000 users, but 4-5 labs do direct submission of a lot of data; he suggested Phenex modified as a web tool to put in data; also ontology modification/use of Mesquite

  • Miscellaneous discussion following above (Tuesday am)
  • Open to communities
    • Phenoscape has public data, but can upload private data and use visualization tool
    • working environment enabling exploration of data for analysis
    • would allow people temporarily to overlay on whole data store
  • NCBI blast similarity – phenoblast
    • Will need term tracker
    • Monte: Issue of best practice for global size/shape
    • Todd: (here is forest of EQs that match)
      • can move up and down ontology
      • shape and syntax; best practice
  • Discussion of images (linked to AO, PATO) – definitional, put in ontology; browsing, finding right AO term
    • could call for images in particular sets of species
  • Are ontologies useful for phylogenetics? ATOL data and relationships are a challenge (Paul)
    • Can a matrix be reconstructed and can data be related in an effective way?
    • Do ontologies serve this community well?
    • Limiting from community?
    • Explore whether useful for phylogenetics?
    • Capability of characters for phylogenetic studies?
  • Viability of PhenoscapeII depends on morphologists using it!
    • vast phylogenetic branches – does character annotation at gross level conceal or reveal phylogenetic information?
    • Can we retrieve the characters that are discordant?
  • What question motivates character matrix?

Developmental time & use case discussion

Wednesday morning

  • Nomenclatural history of terms in ontologies
    • Current exchange format standards don't support this really beyond obsoletion
    • ZFIN tracks within the database the complete nomenclatural history of gene names
    • RDBOM tracks literature and author attribution for anatomy terms but not yet nomenclatural history
  • Character quality profiles for data matrices
    • Addresses the question of "Where in the skeleton are the changes occurring that drive the phylogeny"
    • Distribution of characters across the skeletal anatomy, at different levels of the hierarchy
    • Distribution of missing data across the anatomy, at different hierarchy levels
    • How many taxa have how much missing data, distributed on which anatomical parts
  • Use case: Character redundancy
    • Deriving a character profile across the anatomy could help visualize the redundancy between annotations
  • Use case: Mapping the evolutionary characters that lead (and distinguish) to a model organism. Subsequently, see whether these evolutionary changes and the order in which they appear to the ontogeny of the organism.
    • Will need to deal with character gaps and with character redundancy for this.

Specific goals:

  1. Expand taxonomic coverage of Phenoscape to Vertebrata
    • Mouse is done but needs to be rearranged (MP decomposition)
    • Amniotes need to be done from the ground up

Wednesday afternoon

  • Problem of lossy transformation of legacy character data
    • EQ annotation is often at a lesser granularity (or level of detail) than the original free text description
    • This isn't due to any technological obstacles but rather due to the limited resources available for annotation.
    • Annotation effort is best focused to a granularity level where it suffices to solve a use-case of interest.
    • Annotating at very granular levels is entirely possible but can take a lot of time because many of the ontology terms needed are likely not to be present yet in the ontology.
    • How does this impact phylogeny and data matrix reconciliation, or phylogenetic reconstruction on the basis of the EQ annotations?
  • Use-case for development
    • Heterochrony would be interesting if one can pull it out of the database
    • Developmental ordering relationships currently used are confined to develops_from and transforms-into.
      • This is missing yet for mouse.
      • Wouldn't really allow inferring heterochrony.
      • Would allow though to place and compare the placement of phenotypes into a developmental chain of transformations.
  • Demonstration of Phenoscape KB
    • Some of the features we are developing (the 3 principle queries) would be very useful to MOD users
  • Informatics goals for Phenoscape 2:
    • Supporting units for measurements
    • Allowing others to compare their phenotype data to the knowledge base
    • Generic ontological queries, such as a SPARQL endpoint
    • Private data overlay
    • Linked Data and semweb integration
    • Tree visualization
    • Triple store technology evaluation
    • Species ID
    • Phylogenetically informative distance metric based on EQ assertions
    • NLP-based text processing, Mass curation

Idea bin

  1. Intermine connection (multiple model organisms, AJAX-based widget for displaying protein family tree)
  2. Some phenotypes imply developmental abnormalities, differences, or variation.
    • For example, a "poorly ossified cranium" in an adult amphibian implies that the developmental process was delayed or did not complete.
  3. How does logical inference of homology propagate over develops-from relationships.
    • E.g., if A and B are asserted homologous, and C develops from A and D develops from B, are then C and D inferred as homologous, and are C and B inferred as homologous.