Phenoscape Grant Renewal Workshop/Notes
From phenoscape
Contents
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
- How is this supported in MGI?
- 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.
- Different approaches between MGI and ZFIN:
- Evolutionary developmental data could come from medaka, stickleback
- Sequence of steps:
- 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
- Requirements:
- 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?)
- Mammalian phenotype decomposition
- Need support for QC'ing the results of automated decomposition
- Alignment of MP with mouse anatomy
- Annotation
- Which published character matrices are there for dinosaurs?
- Ontology building
- 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:
- 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
- Intermine connection (multiple model organisms, AJAX-based widget for displaying protein family tree)
- 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.
- 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.
