Reasoning over phenotypediversity, character change, and evolutionary descent                Hilmar LappNational Evolution...
Regier et al (2010                                            Parfrey et al (2010, Parfrey & Katz                       Li...
Large body of evolutionaryphenotype documentation
Chen & Mayden (2010)                                             PhenotypeMabee (2000)                               chang...
Phenotype observationsimportant to many fields                Kimmel et al, 2003
Phenotype observationsimportant to many fields                Kimmel et al, 2003
As complex, free text phenotypes   are resistant to computing              (Lundberg and Akama 2005)
Finding similar information       in free-text is difficult      “lacrymal bone...flat’’          Mayden 1989               ...
Meaning of words      depends on contextMole:•   Burrowing insectivorous mammals in the family Talpidae•   A spy buried se...
What is an ontology?• An ontology is a type of vocabulary  with well-defined terms and the logical  relationships that hold...
Ontologies support reasoning                  • Relationships                    (“assertions”)                    induce ...
The same principles       apply to anatomy                                          pharyngeal                    ventral ...
The same principles apply to anatomy
Integrating across studies?Fig. 7, Sereno (2009)                        Fig. 6, Sereno (2009)
Computing example:Search bySimilarity                                           Fig. 3, Washington et al (2009)         Fi...
Computing example:Search bySimilarity                                                                            Fig. 3, W...
Computing overcomparative morphology?  Cyprinus carpio         Pangio anguillaris        Nemacheilus fasciatusCatostomus c...
Knowledge mining &        hypothesis generation      Model Organism                                             Non-model ...
Phenoscape• Collaboration between P. Mabee (PI, U. South  Dakota), M. Westerfield (ZFIN), and Todd Vision  (UNC, NESCent)• ...
Entity-Quality Model forEvolutionary Phenotypes        Character                 State   Entity          Attribute      Va...
Entity-Quality Model forEvolutionary Phenotypes        Character                 State   Entity          Attribute      Va...
Entity-Quality Model forEvolutionary Phenotypes        Character                   State   Entity          Attribute      ...
Entity-Quality Model forEvolutionary Phenotypes        Character                   State   Entity          Attribute      ...
Taxon phenotype assertion                                  Links a quality to the            Links a taxon to a   entity t...
Taxon phenotype assertion                                  Links a quality to the            Links a taxon to a   entity t...
Gene phenotype assertion                                  Links a quality to the           Links a genotype to a entity th...
Full workflow:              free-text → EQ → integrated KBlegacy free-text                                    EQ = bodychar...
Full workflow:              free-text → EQ → integrated KBlegacy free-text                                    EQ = bodychar...
Phenoscape Knowledgebase
Major taxonomic groups havesimilar distribution of entities      among phenotypes                              25 July 2008
Some notable differences           for skeletal characters    Clupeiformes                                                ...
Substantial overlap between                 model organism and               evolutionary phenotypeshematopoie7c system   ...
Hypothesis generation:    Genetic basis for scale loss in            SiluriformesMutation of eda gene                 Icta...
Wet lab test   (Work by Richard Edmunds)           Ictalurus punctatuseda expression is lacking in the epidermis
Hypothesis generation:  Genetic basis for absence of the   basihyal bone in SiluriformesMutation of brpf1 gene            ...
Wet lab test (Work by Richard Edmunds)        Ictalurus punctatus         78 hpf     86 hpfbrpf1 lacks expression in the b...
The parts to make this work • Ontologies that capture the knowledge   domains • Efficient data curation workflow • Expressiv...
• Teleost Anatomy                                                  (seeded from Zebrafish)                                 ...
Making PATO usable for evolutionary data
Getting ontologies right       is a challenge• What is the right axis of classification?  • Structure versus function  • Re...
Curation                               Dahdul et al., 2010 PLoS ONE           2. Students:                                ...
KB is based on OBD(Ontology-Based Database)                                                          (C. Mungall, LBL)    ...
PATO:quality                       Measurement                    ZFIN:Publication                    ECO:evidence        ...
How does reasoning work?
How does reasoning work?     TTO:                    PATO:rectangular^    PATO:curvature^                     ZFIN:Batroch...
How does reasoning work?                                                                                          TAO:    ...
How does reasoning work?                                                                                                 T...
How does reasoning work?                                                                                                  ...
How does reasoning work?                                                                                                  ...
How does reasoning work?                                                      PATO:shape^                                 ...
How does reasoning work?                                                        PATO:shape^                               ...
How does reasoning work?                                                        PATO:shape^                               ...
How does reasoning work?                                                    PATO:shape^                                   ...
Entity 1       Taxon 1     Relationship         Entity 2         Taxon 2        Evidence       Reference(s)  scaphium     ...
What next?• Modeling and reasoning over  homology• Efficient searching and scoring of  semantic similarity• Reducing the bo...
Opening descriptive biological data to computing can enable new science                   Taxonomy,                  Conse...
Acknowledgements• Phenoscape              • Berkeley Bioinformatics Personnel & PIs:          & Ontologies Project P. Mabe...
Phenotypic similarity matches                taxa to candidate genes                                           Taxon      ...
Mapping EQs back to characters is a challenge• Properties of “good” phylogenetic characters:  • Exclusivity of states  • D...
Which EQs and qualities  are incompatible?• Incompatible Qs        • Compatible Qs  • present vs. absent     • present vs....
Detecting phenotype        change and variation                 Hemiodus argenteus {shape:bent inheres_in supraorbital bon...
System architecture        Knowledgebase User Inteface             External web sites   Web Application for Exploration & ...
Formalizing homology        relationships• Formal pattern is ternary:    E1 in_taxon T1 homologous_to E2 in_taxon T2 as E3...
Option 1: Asserting homology     at higher-level taxa
Option 2: Asserting homology       at species level
Validation through standard     OWL-DL reasoning
Reasoning over phenotype diversity, character change, and evolutionary descent
Reasoning over phenotype diversity, character change, and evolutionary descent
Reasoning over phenotype diversity, character change, and evolutionary descent
Reasoning over phenotype diversity, character change, and evolutionary descent
Reasoning over phenotype diversity, character change, and evolutionary descent
Reasoning over phenotype diversity, character change, and evolutionary descent
Reasoning over phenotype diversity, character change, and evolutionary descent
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Reasoning over phenotype diversity, character change, and evolutionary descent

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Invited department seminar at the University of Florida in Gainesville, March 1, 2011

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Reasoning over phenotype diversity, character change, and evolutionary descent

  1. 1. Reasoning over phenotypediversity, character change, and evolutionary descent Hilmar LappNational Evolutionary Synthesis Center (NESCent) Seminar at University of Florida, March 1, 2011
  2. 2. Regier et al (2010 Parfrey et al (2010, Parfrey & Katz Life has evolved a stunning diversity of phenotypes Images: Web Tree of Life (http://tolweb.org)
  3. 3. Large body of evolutionaryphenotype documentation
  4. 4. Chen & Mayden (2010) PhenotypeMabee (2000) changes inform phylogenetic reconstruction from: Understanding Evolution Sereno (1999)
  5. 5. Phenotype observationsimportant to many fields Kimmel et al, 2003
  6. 6. Phenotype observationsimportant to many fields Kimmel et al, 2003
  7. 7. As complex, free text phenotypes are resistant to computing (Lundberg and Akama 2005)
  8. 8. Finding similar information in free-text is difficult “lacrymal bone...flat’’ Mayden 1989 Grande and Poyato- “lacrimal...small, flat” Ariza 1999 “lacrimal...triangular’’ Royero 1999 “first infraorbital (lachrimal) Kailola 2004 shape...flattened”“fourth infraorbital...anterior and Zanata and Vari 2005 posterior margins...in parallel”
  9. 9. Meaning of words depends on contextMole:• Burrowing insectivorous mammals in the family Talpidae• A spy buried secretly within an organization or country• The SI unit used in chemistry for the amount of a substance• A small, sometimes raised area of skin, usually with darker pigment• A Mexican sauce made from chili peppers and other spices, including chocolate• A massive structure, usually of stone, used as a pier, jetty, or breakwater between places separated by water
  10. 10. What is an ontology?• An ontology is a type of vocabulary with well-defined terms and the logical relationships that hold between them.• An ontology represents the knowledge about its subject domain.
  11. 11. Ontologies support reasoning • Relationships (“assertions”) induce a hierarchical structure. • Ontologies can be processed by machines to make inferences.
  12. 12. The same principles apply to anatomy pharyngeal ventral arch hyoid arch cartilage replacement part_of bone is_a part_of basihyal is_a cartilagebasihyalelement is_a basihyal bone develops_from
  13. 13. The same principles apply to anatomy
  14. 14. Integrating across studies?Fig. 7, Sereno (2009) Fig. 6, Sereno (2009)
  15. 15. Computing example:Search bySimilarity Fig. 3, Washington et al (2009) Fig. 1, Washington et al (2009)
  16. 16. Computing example:Search bySimilarity Fig. 3, Washington et al (2009) Trogloglanis pattersoni - a blind catfish http://tolweb.org/Trogloglanis/69910 Fig. 1, Washington et al (2009)
  17. 17. Computing overcomparative morphology? Cyprinus carpio Pangio anguillaris Nemacheilus fasciatusCatostomus commersoni Gyrinocheilus aymonieri Phenacogrammus interruptus
  18. 18. Knowledge mining & hypothesis generation Model Organism Non-model organisms Mutagenesis Mutation, selection, drift, gene flowMutant or missing protein at Altered expression orspecific developmental stage function of protein Phenotype change(s) Phenotype changes between to wildtype evolutionary lineages middle nuchal plate predorsal spinelet spine anterior nuchal plate Order Siluriformes Laue et al (2008) Pimelodus maculatus 2 cm abdominal Order Characiformes scutes Catoprion mento
  19. 19. Phenoscape• Collaboration between P. Mabee (PI, U. South Dakota), M. Westerfield (ZFIN), and Todd Vision (UNC, NESCent)• Aim: Foster devo-evo synthesis by • Prototyping a database of curated, machine- interpretable evolutionary phenotypes. • Integrating these with mutant phenotypes from model organisms. • Enabling data-mining and discovery for candidate genes of evolutionary phenotype transitions.• Informatics for the project is developed and hosted at NESCent
  20. 20. Entity-Quality Model forEvolutionary Phenotypes Character State Entity Attribute Value ectopterygoid shape rectangular
  21. 21. Entity-Quality Model forEvolutionary Phenotypes Character State Entity Attribute Value ectopterygoid shape rectangular Entity (TAO) Quality (PATO) ectopterygoid rectangular
  22. 22. Entity-Quality Model forEvolutionary Phenotypes Character State Entity Attribute Value ectopterygoid shape rectangular implies Entity (TAO) Quality (PATO) ectopterygoid rectangular
  23. 23. Entity-Quality Model forEvolutionary Phenotypes Character State Entity Attribute Value ectopterygoid shape rectangular implies Entity (TAO) Quality (PATO) }ectopterygoid rectangular Phenotype
  24. 24. Taxon phenotype assertion Links a quality to the Links a taxon to a entity that is its bearer Phenotypic Quality phenotype ontology term some rectangular exhibits some inheres_in some Batrachoglanis raninus ectopterygoid Taxon Anatomyontology term ontology term
  25. 25. Taxon phenotype assertion Links a quality to the Links a taxon to a entity that is its bearer Phenotypic Quality phenotype ontology term some rectangular exhibits some inheres_in some Batrachoglanis raninus ectopterygoid Taxon Anatomyontology term ontology term Evidence Curator Specimen Publication Code
  26. 26. Gene phenotype assertion Links a quality to the Links a genotype to a entity that is its bearer Phenotypic Quality phenotype ontology term curvature influences some inheres_in someedn1tf216b/tf216b maxilla AnatomyGenotype ontology term Publication
  27. 27. Full workflow: free-text → EQ → integrated KBlegacy free-text EQ = bodycharacter data lacks all Taxon Gene Anatomical Entity Quality parts of type anatomical has number Teleostei eda scale structure of is_a is_a is_a is_a Siluriformes is_a body scale lacks allKailola (2004) inheres_in towards parts of type Gasterosteiformes inheres_in towards is_a is_a is_a is_a variant_of inheres_in towards is_a © Jean Ricardo Simões Vitule has fewer body lacks all parts of type Ictalurus punctatus exhibitsmutant phenotype EQ = body parts of type scale Here, we describe the phenotypic and has fewer is_a molecular characterization of a set of parts of type body lacks all mutants showing loss of adult structures of Apeltes quadracus exhibits the dermal skeleton, such as the rays of the scale parts of type scale fins and the scales, as well as the pharyngeal teeth. The mutations represent adult-viable, loss of function alleles in the body has fewer ectodysplasin (eda) and ectodysplasin edadt3S243X/+ influences parts of type scale receptor (edar) genes. Harris et al. (2008)
  28. 28. Full workflow: free-text → EQ → integrated KBlegacy free-text EQ = bodycharacter data lacks all Taxon Gene Anatomical Entity Quality parts of type anatomical has number Teleostei eda scale structure of is_a is_a is_a is_a Siluriformes is_a body scaleKailola (2004) •501,862 taxon phenotype annotations inheres_in towards lacks all parts of type • Gasterosteiformes Curated from 4,732 characters in 2,474 is_a inheres_in towards is_a is_a inheres_in towards is_a species from 52 papers variant_of is_a © Jean Ricardo Simões Vitule has fewer body lacks all parts of type •From ZFIN: 21,829 phenotype annotations scale Ictalurus punctatus exhibitsmutant phenotype EQ = body parts of type has fewer is_a about 3,893 genes Here, we describe the phenotypic and parts of type molecular characterization of a set of mutants showing loss of adult structures of Apeltes quadracus body lacks all exhibits the dermal skeleton, such as the rays of the scale parts of type scale fins and the scales, as well as the pharyngeal teeth. The mutations represent adult-viable, loss of function alleles in the body has fewer ectodysplasin (eda) and ectodysplasin edadt3S243X/+ influences parts of type scale receptor (edar) genes. Harris et al. (2008)
  29. 29. Phenoscape Knowledgebase
  30. 30. Major taxonomic groups havesimilar distribution of entities among phenotypes 25 July 2008
  31. 31. Some notable differences for skeletal characters Clupeiformes  % Postcranial axial skeleton Gonorynchiformes  % Paired fins  Gymno<formes  %  Cranium  Characiformes  Cypriniformes  Image from Sabaj-Perez Siluriformes  0  10  20  30  40  50  60  70  25 July 2008
  32. 32. Substantial overlap between model organism and evolutionary phenotypeshematopoie7c system  •4,217 zebrafish phenotypes reproduc7ve system  •3,405 evolutionary characters musculature system liver and biliary system  respiratory system  renal system  endocrine system  Evolu7onary characters  Zebrafish phenotypes  immune system  diges7ve system  cardiovascular system  skeletal system  sensory system  nervous system  0  500  1000  1500  2000  2500  25 July 2008
  33. 33. Hypothesis generation: Genetic basis for scale loss in SiluriformesMutation of eda gene Ictalurus punctatus:in Danio: Harris et al., 2007 Copyright  ©  Jean  Ricardo  Simões  Vitule,  All  Rights  Reserved
  34. 34. Wet lab test (Work by Richard Edmunds) Ictalurus punctatuseda expression is lacking in the epidermis
  35. 35. Hypothesis generation: Genetic basis for absence of the basihyal bone in SiluriformesMutation of brpf1 gene Ictalurus punctatus:in Danio: Laue et al (2008)
  36. 36. Wet lab test (Work by Richard Edmunds) Ictalurus punctatus 78 hpf 86 hpfbrpf1 lacks expression in the basihyal
  37. 37. The parts to make this work • Ontologies that capture the knowledge domains • Efficient data curation workflow • Expressive and scalable inference engine
  38. 38. • Teleost Anatomy (seeded from Zebrafish) • Teleost TaxonomyOntology (based on Eschmeyer’s Catalog of Fishes)development • Phenotypic QualityDahdul et al (2009), Cover art: K. Luckenbill (PATO)
  39. 39. Making PATO usable for evolutionary data
  40. 40. Getting ontologies right is a challenge• What is the right axis of classification? • Structure versus function • Relational vs monadic qualities • PATO: shape and size vs natural language ”Interopercle shape: expanded posteroventrally”• Different ways to observe or generate a phenotypic quality • Color as color hue (radiation quality) or pigmentation (structural quality) • Relative sizes don’t have a universal reference
  41. 41. Curation Dahdul et al., 2010 PLoS ONE 2. Students: 3. Character Manual entry of free annotation by experts: text character Entry of phenotypes descriptions, matrix, and homology taxon list, specimens assertions using and museum numbers Phenex using Phenex Curators: Wasila Dahdul Miles Coburn Jeff Engemen Terry Grande 1. Students: Eric Hilton gather publications John Lundberg 4. Consistency (scan hard copies, Paula Mabee checks, upload ofproduce OCR PDFs) Richard Mayden data to public view of Mark Sabaj Pérez Phenoscape KB
  42. 42. KB is based on OBD(Ontology-Based Database) (C. Mungall, LBL) Inference_Evidence_Support Link_Cardinality Inference_Evidence_Support_ID Link_ID of link - object_cardinality inferred from link - object_min_cardinality for evidence - object_max_cardinality Link Link_ID Inference_Evidence - combinator Inference_Evidence_ID Node_Xref - is_inferred Alias Node_ID - is_instantiation of link inference type Alias_ID - is_negated - is_obsolete evidence type - scope Xref - is_metadata - label for context - applies_to_all of node - object_quantifier_some synonym - object_quantifier_only source type source Description_Xref subject Description_ID predicate object reified as valid during Xref Node for context Node_ID TagVal - uid Description TagVal_ID - label - val Description_ID - uri - scope - metatype for node - label - is_anonymous of node predicate (tag) - is_transitive - is_obsolete data type description type source - is_reiflink source source
  43. 43. PATO:quality Measurement ZFIN:Publication ECO:evidence curator(s) -value/max/min uid = ZFIN ID -unit OBO_REL:is_a has_measurement OBO_REL:posited_by dc:creator has_evidence TTO:taxon Phenotype Genotype PHENO:exhibits OBO_REL:influencesuid = TTO ID (class expression) uid = ZFIN ID OBO_REL:towards PHENO:asserted_for_otu OBO_REL:inheres_in OBO_REL:variant_of {TAO,ZFA}:entity PHENO:has_taxon uid = {TAO,ZFA} ID OBO_REL:posited_by Gene {TAO,ZFA}:entity uid = ZFIN ID uid = {TAO,ZFA} ID OBO_REL:posited_by CDAO:TU CDAO:CharacterStateDomain name = Publication Taxon CDAO:CharacterStateDatum CDAO:has_State name = state text CDAO:has_TU PHENO:has_comment PHENO:has_comment dwc:individualID CDAO:CharacterStateDataMatrix CDAO:has_Datum comments CDAO:has_Character comment (literal text) CDAO:Character (literal text) name = character text Specimen PHENO:has_publication PHENO:has_comment PHENO:has_comment dwc:catalogID dwc:collectionID PHENO:Publication -dc:abstract publication notes comment -dc:bibliographicCitation (literal text) (literal text) catalog number COLLECTION -dc:date (literal text) Figure 3
  44. 44. How does reasoning work?
  45. 45. How does reasoning work? TTO: PATO:rectangular^ PATO:curvature^ ZFIN:Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla)
  46. 46. How does reasoning work? TAO: dermal bone TAO: is_a palatoquadrate arch PATO:shape part_of is_a part_of TAO:maxilla is_a is_a TAO: is_a ectopterygoid PATO:rectangular PATO:curvature ZFA:maxilla TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  47. 47. How does reasoning work? TAO: dermal bone TAO: is_a palatoquadrate arch PATO:shape part_of is_a part_of TAO:maxilla is_a is_a TAO: is_a ectopterygoid PATO:rectangular PATO:curvature in ZFA:maxilla s_ re is_a is_a he inheres_in in TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  48. 48. How does reasoning work? TAO: is dermal bone _a TAO: is_a palatoquadrate arch pa PATO:shape part_of rt_ is_a of part_of TAO:maxilla is_a is_a TAO: is_a ectopterygoid PATO:rectangular PATO:curvature ZFA:maxilla s _in is_a ere is_a inh inheres_in TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: is_a has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  49. 49. How does reasoning work? TAO: is_ dermal bone a TAO: is_a palatoquadrate arch PATO:shape pa of part_of in rt_ is_a rt_ of res_ pa in_ re s_ inhe is_a e part_of TAO:maxilla inh _in is_a is_a is s _a re TAO: is_a he ectopterygoid of in in PATO:rectangular PATO:curvature rt_ e s_ pa er ZFA:maxilla in i n_ in h re s_ s_ is_a e re is_a inh he inheres_in in TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: is_a has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  50. 50. How does reasoning work? PATO:shape^ inheres_in TAO: is_ (TAO:dermal bone) dermal bone a TAO: is_a palatoquadrate arch PATO:shape PATO:shape^ pa part_of rt_ of in inheres_in_part_of is_a art _ of res_ p (TAO:palatoquadrate arch) s_ in_ re inhe is_a inhe part_of TAO:maxilla is_a is_a _in is_ es TAO: a er is_a inh ectopterygoid f in PATO:rectangular PATO:curvature o s_ rt_ re _ pa he ZFA:maxilla in in in s_ s_ ere e re is_a is_a inh inh inheres_in TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: is_a has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  51. 51. How does reasoning work? PATO:shape^ inheres_in TAO: is_ inheres_in (TAO:dermal bone) dermal bone a TAO: is_a palatoquadrate arch is_a in_pa rt_of PATO:shape^ inheres_ pa PATO:shape part_of rt_ is_a of in inheres_in_part_of is_a art _ of res_ p (TAO:palatoquadrate arch) s_ in_ re inhe is_a inhe part_of TAO:maxilla is_a is_a _in is_ es TAO: a er is_a inh ectopterygoid f in PATO:rectangular PATO:curvature o s_ rt_ re _ pa he ZFA:maxilla in in in s_ s_ ere e re is_a is_a inh inh inheres_in TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: is_a has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  52. 52. How does reasoning work? PATO:shape^ inheres_in TAO: is_ inheres_in (TAO:dermal bone) dermal bone a TAO: is_a is_a is_a palatoquadrate arch _in_pa rt_of PATO:shape^ inheres pa PATO:shape part_of rt_ is_a of in inheres_in_part_of is_a art _ of res_ p (TAO:palatoquadrate arch) s_ in_ re inhe is_a inhe part_of TAO:maxilla is_a is_a is_ _in a is_ is_a es is_a TAO: a er is_a inh ectopterygoid f in PATO:rectangular PATO:curvature o s_ rt_ re _ pa he ZFA:maxilla in in in s_ s_ ere e re is_a is_a inh inh inheres_in TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: is_a has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  53. 53. How does reasoning work? PATO:shape^ inheres_in TAO: is_ inheres_in (TAO:dermal bone) dermal bone a TAO: is_a is_a is_a palatoquadrate arch art_of inher es_in_p PATO:shape PATO:shape^ pa part_of rt_ is_a of in inheres_in_part_of is_a art _ of res_ (TAO:palatoquadrate arch) _p s _in ere inhe is_a inh part_of TAO:maxilla is_a is_a is_ _in a is_ is_a es is_a TAO: a er is_a inh ectopterygoid f in PATO:rectangular PATO:curvature o _ a rt_ r es _p e ZFA:maxilla in in inh s_ _ e r es is_a er e is_a inh inh inheres_in TTO: PATO:rectangular^ PATO:curvature^ ZFIN: Batrochoglanis inheres_in inheres_in influences edn1tf216b/tf216b exhibits raninus (TAO:ectopterygoid) (ZFA:maxilla) is_a variant_of TTO: is_a has_rank TTO: TTO: ZFIN:edn1 Batrochoglanis is_a Pseudopimelodidae TTO:TAXRANK:species has_rank TAXRANK:genus TTO: TAXRANK:family has_rank
  54. 54. Entity 1  Taxon 1  Relationship  Entity 2  Taxon 2  Evidence  Reference(s)  scaphium  Otophysi  homologous_to  neural arch 1  Teleostei   IDS, IMS, IPS   (Fink and Fink,  1981; Rosen and  Greenwood,  1970)  Futureintercalarium  Otophysi  homologous_to  neural arch 2  (ventral  portion)  Teleostei  IDS, IMS, IPS   (Rosen and  Greenwood,  1970)  Directions: 1. (Fink and Fink, intercalarium  Otophysi  homologous_to  neural arch 2   Teleostei  NAS  1981) intercalarium  Otophysi  homologous_to  neural arch 2   Teleostei  IMS  (Hora, 1922) intercalarium  Otophysi  homologous_to  rib of vertebra 2  Teleostei  TAS   (Hora 1922)  (Fink and Fink,  Reasoning parapophysis +  1981; Rosen and  over tripus  Otophysi  homologous_to  Teleostei   IDS, IMS, IPS   rib of vertebra 3  Greenwood,  1970)  homology image by Kyle Luckenbill, ANSP
  55. 55. What next?• Modeling and reasoning over homology• Efficient searching and scoring of semantic similarity• Reducing the bottlenecks in data curation
  56. 56. Opening descriptive biological data to computing can enable new science Taxonomy, Conservation Species ID Biology Biodiversity (Specimens, Occurrence records) Descriptive biology Ecology - Phenotypes - Traits - Function - Behavior - Habitat - Life Cycle - Reproduction Physiology - Conservation Threats Genetics Genomics, Genetic Gene variation expression
  57. 57. Acknowledgements• Phenoscape • Berkeley Bioinformatics Personnel & PIs: & Ontologies Project P. Mabee, (BBOP): M. Westerfield, C.Mungall, S.Lewis T. Vision, J. Balhoff, • National Evolutionary C. Kothari, Synthesis Center W. Dahdul, (NESCent) P. Midford • NSF (DBI 0641025)• Phenoscape curators & workshop participants
  58. 58. Phenotypic similarity matches taxa to candidate genes Taxon CandiateSimilarity Taxon Gene Subsuming (subsuming taxon with phenotype Gene(s) (IC) variable phenotypes in subsumed taxa) (one of two or more subsumed variable taxon (zebrafish) phenotype phenotype phenotypes) Danio rerio: epural epural, epural, 15.16 Danio trpm7 separated from composition structure urostyle Siluriformes: 14.45 Otophysi eda scales, absent scales, count scales, absent Siluriformes: basihyal brpf1, disc1 and basihyal 13.25 Siluriformes basihyal cartilage, 10 more cartilage, absent cartilage, absent count process of Meckel’s Meckel’s Meckel’s cartilage, edn1, foxd3 and cartilage, 10.0 Tachysurus cartilage, adjacent to 22 more mislocalized position coronoid posteriorly process
  59. 59. Mapping EQs back to characters is a challenge• Properties of “good” phylogenetic characters: • Exclusivity of states • Distinguishability of states • Independence of characters• Finding exclusive states requires incompatible phenotypes. How to determine incompatibility? • Two phenotypes are incompatible iff they cannot both inhere in the same specimen. • Two qualities are incompatible iff an entity cannot bear both.
  60. 60. Which EQs and qualities are incompatible?• Incompatible Qs • Compatible Qs • present vs. absent • present vs. any • triangular vs. other quality round (except absent) • absent vs. any • serrated vs. round other quality • some colors• Incompatible EQs • (Q inheres_in bone E) vs (cartilage E absent)
  61. 61. Detecting phenotype change and variation Hemiodus argenteus {shape:bent inheres_in supraorbital bone, count:absent inheres_in upper pharyngeal 5 tooth} {shape:bent inheres_in supraorbital bone,Hemiodus shape:straight inheres_in supraorbital bone, count:absent inheres_in upper pharyngeal 5 tooth, count:present inheres_in upper pharyngeal 5 tooth} {shape:straight inheres_in supraorbital Hemiodus unimaculatus bone, count:present inheres_in upper pharyngeal 5 tooth} {Change in: shape inheres_in supraorbital bone, Change in: count inheres_in upper pharyngeal 5 tooth}
  62. 62. System architecture Knowledgebase User Inteface External web sites Web Application for Exploration & Mining and client (Ruby on Rails, JavaScript) applications Knowledgebase Data Services API (REST) OBD Programming API OBD Reasoner (Java) Teleost Taxonomy Ontology (TTO) Knowledgebase (OBD) (PostgreSQL) Phenotypic Anatomy Quality Ontology Ontologies (PATO) (ZFA, TAO)Genes & genotypes Homology assertions Mutant EQ phenotypes Evolutionary EQ Phenotypes NeXML OBO Library from Zebrafish Model (through annotation) Organism Database Phenex Skeletal Character Data (Evolutionary EQ (from phylogenetic annotation) treatments in literature)
  63. 63. Formalizing homology relationships• Formal pattern is ternary: E1 in_taxon T1 homologous_to E2 in_taxon T2 as E3 in_taxon T3• Classifying homology relationships • 1-1 homology (phylogenetic homology) • serial homology• A iso_homologous_to B as C all A derived_by_descent_from some (C and has_derived_by_descendent some B) and all B derived_by_descent_from some (C and has_derived_by_descendent some A)• shares_ancestor_with as a relation chain: derived_by_descent_from o has_derived_by_descendent
  64. 64. Option 1: Asserting homology at higher-level taxa
  65. 65. Option 2: Asserting homology at species level
  66. 66. Validation through standard OWL-DL reasoning

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