Uberon uses the only_in_taxon method to make relationships such as lactifierous gland only in taxonMammalia and boneonly in taxon Vertebrata. These relations are useful for human users of the ontology, and can be used forconsistency checking within the ontology. For example if the FBbt class “tibia” (representing a segment ofan insect leg) were accidentally placed as a child of UBERON:0000979 tibia, this would be flagged by thereasoner because tibia is a bone, bones are found only in vertebrates, and FBbt is a Drosophila ontology
A merger of multi-species anatomy ontologies
A merger of multi-species anatomy ontologies orAn experiment in knowledge management Biocuration 2013 Chris Mungall, Jim Balhoff, Frederic Bastian, David Blackburn, Aurelie Comte , Wasila Dahdul , Alex Dececchi, Nizar Ibrahim, Suzi Lewis, Paula Mabee, Anne Niknejad, Melissa Haendel
We want to understand gene function across taxa Vertebrata tetrapod limbs Ascidians ampullae Echinodermata tube feet Arthropoda Annelida parapodia MolluscaAnatomy ontologies are used to describe morphological variation
Anatomy ontologies built for one species will not work for others http://ccm.ucdavis.edu/bcancercd/22/mouse_figure.htmlhttp://fme.biostr.washington.edu:8080/FME/index.html
So we build species-specific ontologies FMA is_a (SubClassOf) EHDAA2 part_of develops_from surrounded_by organ system solid organ pharyngeal region respiratory primordium respiratory parenchymatous lung bud system organ lung MA Lower thoracic respiratory lobular organ organ system tract cavity MPO abnormal respiratory thoracic respiratory system morphology system cavity organ pleural sac lung abnormal lung morphology lung abnormal pulmonary acinus morphology pulmonary acinus abnormal pulmonary lung alveolus morphology alveolar sac alveolus
But this results in silos FMA is_a (SubClassOf) EHDAA2 part_of develops_from surrounded_by organ system solid organ pharyngeal region respiratory primordium respiratory parenchymatous lung bud system organ lung MA Lower thoracic respiratory lobular organ organ system tract cavity MPO abnormal respiratory thoracic respiratory system morphology system cavity organ pleural sac lung abnormal lung morphology lungabnormal pulmonary acinus morphology pulmonary acinus abnormal pulmonary lung alveolus morphology alveolar sac alveolus
Why not just map ontology terms?Class A Class B Mapped? Useful?FMA: extensor MouseAnatomy: retina Yes Noretinaculum of wristVivo: legal decision Cognitive Atlas: decision Yes NoPlantOntology: Pith MouseAnatomy: medulla Yes NoTaxRank: domain NCI: protein domain Yes NoZfishAnat: hypophysis MouseAnatomy: pituitary No YesTAO:fossa AdverseReactions: depression Yes NoFMA: colon GAZ: Colón, Panama Yes NoQuality: male Chebi: maleate 2(-) Yes NoString matching for mapping can lead to spurious results andsemantics of mappings and provenance are not always clear
Avoiding Silo-izationUse ontologies that are: open documented reusable interoperable built according to shared principles reuse core relations and patternsProblem: How do we re-use in the presence of variability?
Long ago in the world of anatomies CARO FMA EMAP EHDAA2 MA (mostly) FBbt embryonic embryonic XAO ZFA Adult adultDrosophila mouse human Xenopus zebrafish mouse human An anatomical reference ontology was built to help standardize species-specific ontologies
And then came Uberon, created to bridge model organism anatomies CARO UBERON FMA EMAP EHDAA2 MA (mostly) FBbt embryonic embryonic XAO ZFA Adult adultDrosophila mouse human Xenopus zebrafish mouse human
Subsumption of species-specific classes is_a (SubClassOf) anatomical part_of structure develops_from capable_of is_a (taxon equivalent) endoderm only_in_taxon organ part foregut swim bladder organ endoderm of forgut NCBITaxon: respiration organ Actinopterygii respiratory primordium GO: respiratory gaseous exchange pulmonary acinus alveolus lung lung primordiumNCBITaxon: Mammalia alveolus of lung alveolar sac lung bud FMA: pulmonary FMA:lung MA:lung alveolus EHDAA: MA:lung alveolus lung bud Mungall, C. J., Torniai, C., Gkoutos, G. V., Lewis, S. E., & Haendel, M. A. (2012). http://genomebiology.com/2012/13/1/R5
Uberon UBERON includes the cerebellum p pCell Ontology cerebellar cerebellum i to enable i vermis posterior lobequery across i i granularity cerebellum i i cerebellum p p p pposterior cerebellum cerebellar vermis of lobe of posterior vermis cereblleum cerebellum lobe MA:mouse p FMA:human p dendrite dendrite CL:Purkinje cell CL:Purkinje cell axon axon GO/NIF: subcellular GO/NIF: subcellular
Use of Uberon Annotation extensions GOA/UniProtKB [Chris’ talk] Construction of GO terms [Heikos talk] Bgee cross-model homology-based expression search [Frederic’s talk] Annotation of biospecimens from diverse taxa [eagle-i.org] Phenotype similarity analyses to identify disease gene candidates and models New project “Monarch Initiative” to build tools and services for navigating phenotypes [see our poster tonight] PhenoDigm analysis engine [Damian’s talk tomorrow]
Fossils, the ultimate silo Modern diversity only a fraction ofevolutionary diversity Missing evolutionary transitions e.g.fin to limb Extant ontologies not always Shubin et al. 2006compatible with fossil data Different data sources and resolutionbetween extinct and extant
And so over time… CARO UBERON vHOG Arthropod Vertebrate Homologous Organs Group HAO AAO TAOHymenoptera VSAO Amphibian Teleost Vertebrate Skeletal FMA EMAP EHDAA2 MA (mostly) FBbt embryonic embryonic XAO ZFA Adult adult Drosophila mouse human Xenopus zebrafish mouse human … additional multi-species ontologies evolved
But… CARO UBERON vHOG Arthropod Vertebrate Homologous Organs Group HAO AAO TAOHymenoptera VSAO Amphibian Teleost Vertebrate Skeletal FMA EMAP EHDAA2 MA (mostly) FBbt embryonic embryonic XAO ZFA Adult adult Drosophila mouse human Xenopus zebrafish mouse human …they had a hard time maintaining relationships to one another
The big roll-up CARO UBERON-ext Uberon core CL Cell Ontology VSAO AAO TAO Vertebrate Skeletal Amphibian Teleost FMA EMAP EHDAA2 MA (mostly) embryonic embryonic XAO ZFAAdult adult mouse human Xenopus zebrafishmouse human
The new Uberon-ext Contents: – Over 8,000 classes (terms), 2500+ added by Phenoscape – Multiple relationships, including subclass, part-of and develops- from Scope: metazoa (animals) – Current focus is chordates – Includes teleost, amniote, and amphibian specific classes Uberon classes are generic / species neutral – ‘mammary gland’: you can use this class for any mammal! – ‘lung’: you can use this class for any vertebrate (that has lungs)http://purl.obolibrary.org/obo/uberon/ext.obohttp://purl.obolibrary.org/obo/uberon/ext.owl
Managing variation: using reasoners to detect errors only_in_taxon UBERON: bone Vertebrata disjoint with is_a is_aDrosophila melanogaster UBERON: tibia Homo sapiens is_a is_a ✗ part_of part_of Fruit fly FBbt ‘tibia’ Human FMA ‘tibia’ Developmental Biology, Scott Gilbert, 6th ed.
What can you do with the new uberon-ext? kb.phenoscape.org Reason across anatomical variation in extinct and extant taxa Query for candidate genes relevant to morphological evolution Modified from Ahn and Ho 2008
Different strokes for different folksontology contentsbasic simple relationshipshttp://purl.obolibrary.org/obo/uberon/basic.owluberon main ontology http://purl.obolibrary.org/obo/uberon.owlmerged main ontology + links to GO, CL, NCBITaxon, NBOhttp://purl.obolibrary.org/obo/uberon/merged.owlComposite- Uberon plus species-specific ontology classes merged inmetazoan http://purl.obolibrary.org/obo/uberon/composite-metazoan.owlUberon-ext Uberon merged plus TAO, AAO and VSAO terms merged in http://purl.obolibrary.org/obo/uberon/ext.owl Formats:http://uberon.org OBO-Format OWL
Conclusions Model organism anatomies were difficult to query across Uberon was developed to help integrate human and model organism anatomy Uberon has been useful to align model organism anatomy ontologies Palaeontolosts and evo-devo biologists needed wider coverage A core set of vertebrate terms was needed by all=> So we merged the ontologies, and now we can havedinosaur bone data, model organism data, and humandata all integrated and queryable in one database!
Thanks! Chris Mungall, JimBalhoff, Frederic Bastian, David Blackburn, Aurelie Comte , Wasila Dahdul , Alex Dececchi, Nizar Ibrahim, Suzi Lewis, Paula Mabee, Anne Niknejad
Looking for a post-doc? http://nescent.org/about/employment.php#PostDoc2We are recruiting a postdoc with training in bioinformatics who is interested in studyingphenotypic evolution by combining model organism genetic data with comparativeanatomical data from throughout the vertebrates. Projects may range from primarilycomputational to primarily biological.
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