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Biomedical ontology tutorial_atlanta_june2011_part2

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  • http://dbpedia.org/fct/images/lod-datasets_2009-03-27_colored.png
  • http://bioportal.bioontology.org/visualize/42182/?id=HP:0000001#mappings accessed 1/25/2010
  • http://bioportal.bioontology.org/visualize/42182/?id=HP:0000001#mappings accessed 1/25/2010
  • http://bioportal.bioontology.org/visualize/42182/?id=HP:0000001#mappings accessed 1/25/2010
  • http://bioportal.bioontology.org/visualize/42182/?id=HP:0000001#mappings accessed 1/25/2010
  • * = dedicated NIH funding
  • * = dedicated NIH funding
  • with thanks to Robert Arp
  • with thanks to Robert Arp
  • lower lever of types does not ‘carry identity’ in OntoClean terms
  • with thanks to Robert Arp
  • your colors make this slide unreadable on my machine;’ to enable their own existence’ is clumsy English, another  some other
  • power = capability? ‘power’ normally means social power
  • italicize ‘t’ for time
  • Answer the following questions.
  • http://books.google.co.uk/books?id=EqEa2hf7U2AC&pg=PA459&lpg=PA459&dq=a+heart+disease+that+comes+in+successive+phases&source=bl&ots=1pbSgZIa8u&sig=Zp0OwNJjeniJi-KbMOjQ5_v3w-o&hl=en&ei=vPx7S566EIv60wSg9eXYBQ&sa=X&oi=book_result&ct=result&resnum=4&ved=0CBMQ6AEwAw#v=snippet&q=late&f=false

Transcript

  • 1. Basic Building Blocks for Biomedical Ontologies Barry Smith 1
  • 2. Problems with UMLS-style approaches• let a million ontologies bloom, each one close to the terminological habits of its authors• in concordance with the “not invented here” syndrome• then map these ontologies, and use these mappings to integrate your different pots of data 2
  • 3. Mappings are hardThey create an N2 problem; are fragile, and expensive to maintainNeed new authorities to maintain(one for each pair of mapped ontologies), yielding new risk of forking – who will police the mappings?The goal should be to minimize the need for mappings, by avoiding redundancy in the first place – one ontology for each domainInvest resources in disjoint ontology modules which work well together – reduce need for mappings to minimum possible 8
  • 4. Why should you care?• you need to create systems for data mining and text processing which will yield useful digitally coded output• if the codes you use are constantly in need of ad hoc repair huge, resources will be wasted• serious investment in annotation will be defeated from the start• relevant data will not be found, because it will be lost in multiple semantic cemeteries 9
  • 5. How to do it right?• how create an incremental, evolutionary process, where what is good survives, and what is bad fails• where the number of ontologies needing to be used together is small – integration = addition• where these ontologies are stable• by creating a scenario in which people will find it profitable to reuse ontologies, terminologies and coding systems which have been tried and tested 10
  • 6. Reasons why GO has been successfulIt is a system for prospective standardization built with coherent top level but with content contributed and monitored by domain specialistsBased on community consensusUpdated every nightClear versioning principles ensure backwards compatibility; prior annotations do not lose their valueInitially low-tech to encourage users, with movement to more powerful formal approaches (including OWL-DL – though still proceeding caution) 11
  • 7. GO has learned the lessons of successful cooperation• Clear documentation• The terms chosen are already familiar• Fully open source (allows thorough testing in manifold combinations with other ontologies)• Subjected to considerable third-party critique• Tracker for user input and help desk with rapid turnaround 12
  • 8. GO has been amazingly successful in overcoming the data balkanization problembut it covers only generic biological entities ofthree sorts: – cellular components – molecular functions – biological processes no diseases, symptoms, disease biomarkers, protein interactions, experimental processes … 13
  • 9. CONTINUANT OCCURRENT RELATION TO TIME INDEPENDENT DEPENDENTGRANULARITY Anatomical Organism Organ ORGAN AND Entity (NCBI Function ORGANISM (FMA, Taxonomy) (FMP, CPRO) Phenotypic Biological CARO) Quality Process (PaTO) (GO) CELL AND Cellular Cellular Cell CELLULAR Component Function (CL) COMPONENT (FMA, GO) (GO) Molecule Molecular Function Molecular Process MOLECULE (ChEBI, SO, (GO) (GO) RnaO, PrO)OBO (Open Biomedical Ontology) Foundry proposal (Gene Ontology in yellow) 14
  • 10. CONTINUANT OCCURRENT RELATION TO TIME INDEPENDENT DEPENDENTGRANULARITY Environment Ontology Anatomical Organism Organ ORGAN AND Entity (NCBI Function ORGANISM (FMA, Taxonomy) (FMP, CPRO) Phenotypic Biological CARO) (ENVO) Quality Process (PaTO) (GO) CELL AND Cellular Cellular Cell CELLULAR Component Function (CL) COMPONENT (FMA, GO) (GO) Molecule Molecular Function Molecular Process MOLECULE (ChEBI, SO, (GO) (GO) RnaO, PrO) Environment Ontology 15
  • 11. CONTINUANT OCCURRENT RELATION TO TIME INDEPENDENT DEPENDENTGRANULARITY COMPLEX OF Family, Community, Population Population ORGANISMS Deme, Population Phenotype Process Anatomical Organ ORGAN AND Organism Entity Function ORGANISM (NCBI (FMA, (FMP, CPRO) Phenotypic Taxonomy) Biological CARO) Quality Process (PaTO) (GO) CELL AND Cellular Cellular Cell CELLULAR Component Function (CL) COMPONENT (FMA, GO) (GO) Molecule Molecular Function Molecular Process MOLECULE (ChEBI, SO, (GO) (GO) RnaO, PrO) Population-level ontologies 16
  • 12. The OBO Foundry: a step-by-step, evidence-based approach to expanding the GO Developers commit to working to ensure that, for each domain, there is community convergence on a single ontology and agree in advance to collaborate with developers of ontologies in adjacent domains. http://obofoundry.org 17
  • 13. OBO Foundry Principles Common governance (coordinating editors) Common training Common architecture: • simple shared top level ontology (BFO) • shared Relation Ontology: www.obofoundry.org/ro 18
  • 14. Open Biomedical Ontologies Foundry Seeks to create high quality, validated terminology modules across all of the life sciences which will be• one ontology for each domain, so no need for mappings• close to language use of experts• evidence-based• incorporate a strategy for motivating potential developers and users• revisable as science advances 19
  • 15. Principleshttp://obofoundry.org/wiki/index.php/OBO_FoundryPrincip 20
  • 16. RELATION TO CONTINUANT OCCURRENT TIMEGRANULARITY INDEPENDENT DEPENDENT Anatomical Organism Organ Organism-Level ORGAN AND Entity (NCBI Function Process ORGANISM (FMA, Taxonomy) (FMP, CPRO) Phenotypic (GO) CARO) Quality (PaTO) CELL AND Cellular Cellular Cell Cellular Process CELLULAR Component Function (CL) (GO) COMPONENT (FMA, GO) (GO) Molecule Molecular Molecular Function MOLECULE (ChEBI, SO, Process (GO) RnaO, PrO) (GO) OBO Foundry coverage 21
  • 17. ORTHOGONALITYmodularity ensures • annotations can be additive • division of labor amongst domain experts • high value of training in any given module • lessons learned in one module can benefit work on other modules • incentivization of those responsible for individual modules 22
  • 18. Benefits of coordination• Can more easily reuse what is made by others• Can more easily inspect and criticize what is made by others• Leads to innovations (e.g. Mireot strategy for importing terms into ontologies) 23
  • 19. CONTINUANT OCCURRENT RELATION TO TIME INDEPENDENT DEPENDENTGRANULARITY Anatomical Organism Entity Organ ORGAN AND (NCBI (FMA, Function ORGANISM Taxonomy) CARO) (FMP, CPRO) Phenotypic Biological Quality Process XAO ZFA (PaTO) (GO) CELL AND Cellular Cellular Cell CELLULAR Component Function (CL) COMPONENT (FMA, GO) (GO) Molecule (SO, RnaO) Molecular Molecular Function MOLECULE Process ChEBI PRO (GO) (GO) Current Foundry members in yellow 24
  • 20. Foundry ontologies currently underreviewPlant Ontology (PO)Ontology for Biomedical Investigations (OBI)Ontology for General Medical Science (OBMS)Infectious Disease Ontology (IDO) 25
  • 21. top level Basic Formal Ontology (BFO) Information Artifact Ontology for Biomedical Ontology of General mid-level Ontology Investigations Medical Science (IAO) (OBI) (OGMS) Anatomy Ontology (FMA*, CARO) Infectious Disease Environment Ontology Cellular Cell Ontology (IDO*) Component Ontology (EnvO) Ontologydomain level (CL) (FMA*, GO*) Phenotypic Biological Quality Process Ontology Ontology (GO*) Subcellular Anatomy Ontology (SAO) (PaTO) Sequence Ontology (SO*) Molecular Function Protein Ontology (GO*) (PRO*) OBO Foundry Modular Organization 26
  • 22. OBIThe Ontology for Biomedical Investigations hfp://purl.org/obo/OBI_0000225 27
  • 23. Purpose of OBITo provide a resource for the unambiguousdescription of the components ofbiomedical investigations such as thedesign, protocols and instrumentation,material, data and types of analysis andstatistical tools applied to the data NOT designed to model biology 28
  • 24. OBI Collaborating CommunitiesCrop sciences Generation Challenge Programme (GCP),Environmental genomics MGED RSBI Group, www.mged.org/Workgroups/rsbiGenomic Standards Consortium (GSC), www.genomics.ceh.ac.uk/genomecatalogueHUPO Proteomics Standards Initiative (PSI), psidev.sourceforge.netImmunology Database and Analysis Portal, www.immport.orgImmune Epitope Database and Analysis Resource (IEDB), http://www.immuneepitope.org/home.doInternational Society for Analytical Cytology, http://www.isac-net.org/Metabolomics Standards Initiative (MSI),Neurogenetics, Biomedical Informatics Research Network (BIRN),Nutrigenomics MGED RSBI Group, www.mged.org/Workgroups/rsbiPolymorphismToxicogenomics MGED RSBI Group, www.mged.org/Workgroups/rsbiTranscriptomics MGED Ontology Group 29
  • 25. 30
  • 26. 31
  • 27. 32
  • 28. 33
  • 29. Ontology for General Medical Science http://code.google.com/p/ogms/(OBO) http://purl.obolibrary.org/obo/ogms.obo(OWL) http://purl.obolibrary.org/obo/ogms.owl 34
  • 30. OGMS-based initiativesVital Signs Ontology (VSO) (Welch Allyn)EHR / Demographics OntologyInfectious Disease OntologyMental Health Ontology Emotion Ontology 35
  • 31. Ontology for General Medical ScienceJobst Landgrebe (then Co-Chair of the HL7Vocabulary Group):“the best ontology effort in the wholebiomedical domain by far” 36
  • 32. EXPERIMENTAL ARTIFACTS Ontology for Biomedical Investigations (OBI) CLINICAL MEDICINE Ontology of General Medical Science (OGMS)INFORMATION ARTIFACTS Information Artifact Ontology (IAO) How to keep clear about the distinction • processes of observation, • results of such processes (measurement data) • the entities observed 37
  • 33. How is the OBO Foundry organized? • Top-Level: Basic Formal Ontology (BFO) • Mid-Level: IAO, OBI, OGMS ... • Domain-Level: Foundry Bio-Ontologies 38
  • 34. top level Basic Formal Ontology (BFO) Information Artifact Ontology for Biomedical Ontology of General mid-level Ontology Investigations Medical Science (IAO) (OBI) (OGMS) Anatomy Ontology (FMA*, CARO) Infectious Disease Environment Ontology Cellular Cell Ontology (IDO*) Component Ontology (EnvO) Ontologydomain level (CL) (FMA*, GO*) Phenotypic Biological Quality Process Ontology Ontology (GO*) Subcellular Anatomy Ontology (SAO) (PaTO) Sequence Ontology (SO*) Molecular Function Protein Ontology (GO*) (PRO*) OBO Foundry Modular Organization 39
  • 35. BFO: the very top Continuant Occurrent (Process, Event)Independent Dependent Continuant Continuant 40
  • 36. CONTINUANT OCCURRENT RELATION TO TIME INDEPENDENT DEPENDENTGRANULARITY Anatomical Organism Organ ORGAN AND Entity (NCBI Function ORGANISM (FMA, Taxonomy) (FMP, CPRO) Phenotypic Biological CARO) Quality Process (PaTO) (GO) CELL AND Cellular Cellular Cell CELLULAR Component Function (CL) COMPONENT (FMA, GO) (GO) Molecule Molecular Function Molecular Process MOLECULE (ChEBI, SO, (GO) (GO) RnaO, PrO) 41
  • 37. RELATION CONTINUANT OCCURRENT TO TIMEGRANULARITY INDEPENDENT DEPENDENT Anatomical Organism Organ Organism-Level ORGAN AND Entity (NCBI Function Process ORGANISM (FMA, Taxonomy) (FMP, CPRO) Phenotypic (GO) CARO) Quality (PaTO) CELL AND Cellular Cellular Cell Cellular Process CELLULAR Component Function (CL) (GO) COMPONENT (FMA, GO) (GO) Molecule Molecular Molecular Function MOLECULE (ChEBI, SO, Process (GO) RnaO, PrO) (GO) obofoundry.org 42
  • 38. BFO & GO continuant occurrentindependent dependent continuant continuant cellular molecular biologicalcomponent function processes 43
  • 39. Basic Formal Ontologytypes Continuant Occurrent process, event Independent Dependent Continuant Continuant thing quality .... ..... .......instances 44
  • 40. Experience with BFO in building ontologies provides• a community of skilled ontology developers and users (user group has 120 members)• associated logical tools• documentation for different types of users• a methodology for building conformant ontologies by starting with BFO and populating downwards 45
  • 41. Example: The Cell Ontology
  • 42. How to build an ontologyimport BFO into ontology editor such as Protégéwork with domain experts to create an initial mid- level classificationfind ~50 most commonly used terms corresponding to types in realityarrange these terms into an informal is_a hierarchy according to this universality principle A is_a B ≡ every instance of A is an instance of Bfill in missing terms to give a complete hierarchy(leave it to domain experts to populate the lower levels of the hierarchy) 47
  • 43. Users of BFOPharmaOntology (W3C HCLS SIG)MediCognos / Microsoft HealthvaultCleveland Clinic Semantic Database in Cardiothoracic SurgeryMajor Histocompatibility Complex (MHC) Ontology (NIAID)Neuroscience Information Framework Standard (NIFSTD) and Constituent OntologiesInterdisciplinary Prostate Ontology (IPO)Nanoparticle Ontology (NPO): Ontology for Cancer Nanotechnology ResearchNeural Electromagnetic Ontologies (NEMO)ChemAxiom – Ontology for Chemistry 49 :.
  • 44. Users of BFOGO Gene OntologyCL Cell OntologySO Sequence OntologyChEBI Chemical OntologyPATO Phenotype (Quality) OntologyFMA Foundational Model of Anatomy OntologyChEBI Chemical Entities of Biological InterestPRO Protein OntologyPlant OntologyEnvironment OntologyOntology for Biomedical InvestigationsRNA Ontology 50 :.
  • 45. Users of BFOOntology for Risks Against Patient Safety (RAPS/REMINE)eagle-i an VIVO (NCRR)IDO Infectious Disease Ontology (NIAID)National Cancer Institute Biomedical Grid Terminology (BiomedGT)US Army Biometrics OntologyUS Army Command and Control OntologySleep Domain OntologySubcellular Anatomy Ontology (SAO)Translaftional Medicine On (VO)Yeast Ontology (yOWL)Zebrafish Anatomical Ontology (ZAO) 51 :.
  • 46. Basic Formal Ontology continuant occurrentindependent dependent continuant continuant organism 54
  • 47. Continuants• continue to exist through time, preserving their identity while undergoing different sorts of changes• independent continuants – objects, things, ...• dependent continuants – qualities, attributes, shapes, potentialities ... 55
  • 48. Occurrents• processes, events, happenings – your life – this process of accelerated cell division 56
  • 49. Qualitiestemperatureblood pressuremass... are continuants they exist through time while undergoing changes 57
  • 50. Qualitiestemperature / blood pressure / mass ... are dimensions of variation within the structure of the entity a quality is something which can change while its bearer remains one and the same 58
  • 51. A Chart representing howJohn’s temperature changes 59
  • 52. A Chart representing howJohn’s temperature changes 60
  • 53. BFO: The Very Top continuant occurrentindependent dependent continuant continuant quality temperature 62
  • 54. Blinding Flash of the Obviousindependent dependent continuant continuant qualityorganism temperature types John’s John temperature instances 63
  • 55. Blinding Flash of the Obviousindependent dependent continuant continuant qualityorganism temperature types John’s John temperature instances 64
  • 56. Blinding Flash of the Obvious inheres_in .organism temperature types John’s John temperature instances 65
  • 57. temperature types37ºC 37.1ºC 37.2ºC 37.3ºC 37.4ºC 37.5ºCinstantiates instantiates instantiates instantiates instantiates instantiates at t1 at t2 at t3 at t4 at t5 at t6 John’s temperature instances 66
  • 58. human typesembryo fetus neonate infant child adult instantiates instantiates instantiates instantiates instantiates instantiates at t1 at t2 at t3 at t4 at t5 at t6 John instances 67
  • 59. Temperature subtypesDevelopment-stage subtypesare threshold divisions (hence we donot have sharp boundaries, and wehave a certain degree of choice, e.g. inhow many subtypes to distinguish,though not in their ordering) 68
  • 60. independent dependent continuant continuant qualityorganism temperature types John’s John temperature instances 69
  • 61. independent dependent occurrent continuant continuant quality processorganism course of temperature temperature changes John’s John’s John temperature temperature history 70
  • 62. independent dependent occurrent continuant continuant quality processorganism temperature life of an organism John’s John’s John temperature life 71
  • 63. BFO: The Very Top continuant occurrentindependent dependent continuant continuant quality disposition 72
  • 64. BFO: The Very Top continuant occurrentindependent dependent continuant continuant quality function role disposition 73
  • 65. disposition- of a glass vase, to shatter if dropped- of a human, to eat- of a banana, to ripen- of John, to lose hair 74
  • 66. dispositionif it ceases to exist, then its bearerand/or its immediate surroundingenvironment is physically changedits realization occurs when its bearer is insome special physical circumstancesits realization is what it is in virtue of thebearer’s physical make-up 75
  • 67. independent dependent occurrent continuant continuant function process eye to see process of seeingJohn’s eye function of John’s John seeing eye: to see 80
  • 68. OGMS Ontology for General Medical Sciencehttp://code.google.com/p/ogms 88
  • 69. R T U New York State Center of Excellence in Bioinformatics & Life Sciences Ontology of General Medical Science (OGMS)• ontology for the representation of – diseases, signs, symptoms – clinical processes – diagnosis, treatment and outcomes• fundamental idea: – a disease is a disposition rooted in some (physical) disorder in the organism 89
  • 70. R T U New York State Center of Excellence in Bioinformatics & Life Sciences Motivation• Clarity about: – disease etiology and progression – disease and the diagnostic process – phenotype and signs/symptoms – entities in reality and observations of sucn entities 90
  • 71. Physical Disorder 91
  • 72. Physical Disorder– independent continuant fiat object part A causally linked combination of physical components of the extended organism that is clinically abnormal. 92 :.
  • 73. Clinically abnormal– (1) not part of the life plan for an organism of the relevant type (unlike aging or pregnancy),– (2) causally linked to an elevated risk either of pain or other feelings of illness, or of death or dysfunction, and– (3) such that the elevated risk exceeds a certain threshold level.**Compare: baldness 93
  • 74. Big Picture 94
  • 75. Pathological Process=def. A bodily process that is amanifestation of a disorder and is clinicallyabnormal.Disease =def. – A disposition to undergopathological processes that exists in anorganism because of one or moredisorders in that organism. 95
  • 76. Cirrhosis - environmental exposure• Etiological process - phenobarbitol-induced hepatic cell death – produces• Disorder - necrotic liver – bears• Disposition (disease) - cirrhosis – realized_in• Pathological process - abnormal tissue repair with cell proliferation and fibrosis that exceed a certain threshold; hypoxia-induced cell death – produces• Abnormal bodily features – recognized_as• Symptoms - fatigue, anorexia• Signs - jaundice, enlarged spleen 96
  • 77. Dispositions and Predispositions All diseases are dispositions; not all dispositions are diseases. Predisposition to Disease =def. – A disposition in an organism that constitutes an increased risk of the organism’s subsequently developing some disease. 97
  • 78. HNPCC - genetic pre-disposition• Etiological process - inheritance of a mutant mismatch repair gene – produces• Disorder - chromosome 3 with abnormal hMLH1 – bears• Disposition (disease) - Lynch syndrome – realized_in• Pathological process - abnormal repair of DNA mismatches – produces• Disorder - mutations in proto-oncogenes and tumor suppressor genes with microsatellite repeats (e.g. TGF-beta R2) – bears• Disposition (disease) - non-polyposis colon cancer – realized in• Symptoms (including pain) 98
  • 79. Huntington’s Disease - genetic• Etiological process - inheritance of  Symptoms & Signs >39 CAG repeats in the HTT gene  used_in – produces  Interpretive process• Disorder - chromosome 4 with  produces abnormal mHTT – bears  Hypothesis - rule out Huntington’s• Disposition (disease) - Huntington’s  suggests disease  Laboratory tests – realized_in  produces• Pathological process - accumulation of mHTT protein fragments, abnormal  Test results - molecular detection of transcription regulation, neuronal cell the HTT gene with >39CAG repeats death in striatum  used_in – produces  Interpretive process• Abnormal bodily features  produces – recognized_as  Result - diagnosis that patient X has a• Symptoms - anxiety, depression disorder that bears the disease• Signs - difficulties in speaking and Huntington’s disease swallowing 99
  • 80. HNPCC - genetic pre-disposition• Etiological process - inheritance of a mutant mismatch repair gene – produces• Disorder - chromosome 3 with abnormal hMLH1 – bears• Disposition (disease) - Lynch syndrome – realized_in• Pathological process - abnormal repair of DNA mismatches – produces• Disorder - mutations in proto-oncogenes and tumor suppressor genes with microsatellite repeats (e.g. TGF-beta R2) – bears• Disposition (disease) - non-polyposis colon cancer 100
  • 81. Cirrhosis - environmental exposure• Etiological process - phenobarbitol-  Symptoms & Signs induced hepatic cell death  used_in – produces  Interpretive process  produces• Disorder - necrotic liver – bears  Hypothesis - rule out cirrhosis  suggests• Disposition (disease) - cirrhosis  Laboratory tests – realized_in  produces• Pathological process - abnormal tissue  Test results - elevated liver enzymes repair with cell proliferation and in serum fibrosis that exceed a certain  used_in threshold; hypoxia-induced cell death  Interpretive process – produces  produces• Abnormal bodily features  Result - diagnosis that patient X has a – recognized_as disorder that bears the disease• Symptoms - fatigue, anorexia cirrhosis• Signs - jaundice, splenomegaly 101
  • 82. Systemic arterial hypertension• Etiological process – abnormal  Symptoms & Signs reabsorption of NaCl by the kidney  used_in – produces  Interpretive process  produces• Disorder – abnormally large scattered molecular aggregate of salt in the  Hypothesis - rule out hypertension blood  suggests – bears  Laboratory tests  produces• Disposition (disease) - hypertension – realized_in  Test results -  used_in• Pathological process – exertion of abnormal pressure against arterial wall  Interpretive process  produces – produces  Result - diagnosis that patient X has a• Abnormal bodily features disorder that bears the disease hypertension – recognized_as• Symptoms - headaches, dizziness• Signs – elevated blood pressure 102
  • 83. Type 2 Diabetes Mellitus• Etiological process –  Symptoms & Signs – produces  used_in• Disorder – abnormal pancreatic beta  Interpretive process cells and abnormal muscle/fat cells  produces – bears  Hypothesis - rule out diabetes mellitus• Disposition (disease) – diabetes  suggests mellitus  Laboratory tests – fasting serum blood – realized_in glucose, oral glucose challenge test, and/or• Pathological processes – diminished blood hemoglobin A1c insulin production , diminished  produces muscle/fat uptake of glucose  Test results - – produces  used_in• Abnormal bodily features  Interpretive process – recognized_as  produces• Symptoms – polydipsia, polyuria,  Result - diagnosis that patient X has a polyphagia, blurred vision disorder that bears the disease type 2 diabetes mellitus• Signs – elevated blood glucose and hemoglobin A1c 103
  • 84. Type 1 hypersensitivity to penicillin• Etiological process – sensitizing of mast cells and basophils during exposure to  Symptoms & Signs  used_in penicillin-class substance – produces  Interpretive process  produces• Disorder – mast cells and basophils with epitope-specific IgE bound to Fc epsilon  Hypothesis -  suggests receptor I – bears  Laboratory tests –  produces• Disposition (disease) – type I hypersensitivity  Test results – occasionally, skin testing  used_in – realized_in•  Interpretive process Pathological process – type I  produces hypersensitivity reaction – produces  Result - diagnosis that patient X has a disorder that bears the disease type 1• Abnormal bodily features hypersensitivity to penicillin – recognized_as• Symptoms – pruritis, shortness of breath• Signs – rash, urticaria, anaphylaxis 104
  • 85. 105
  • 86. Disease vs. Disease courseDisease =def. – A disposition to undergopathological processes that exists in anorganism because of one or moredisorders in that organism.Disease course =def. – The aggregate ofprocesses in which a disease dispositionis realized. 106
  • 87. coronary heart disease disease associated disease disease with early associated with associated lesions and asymptomatic with surface unstable stablesmall fibrous (‘silent’) disruption of angina angina plaques infarction plaque instantiates instantiates instantiates instantiates instantiates at t1 at t2 at t3 at t4 at t5 John’s coronary heart disease 107 time
  • 88. independent dependent occurrent continuant continuant disposition process disorder course of disease disease John’s John’sdisordered coronary heart course of John’s heart disease disease 108
  • 89. Examples of ontology terms OGMS IDOIndependent Infectious DisorderContinuant disorder Infectious Disease diseaseDependentContinuant Predisposition to Protective disease resistance InfectiousOccurrent Disease course disease course
  • 90. IDO (Infectious Disease Ontology) Core Follows GO strategy of providing a canonical ontology of what is involved in every infectious disease – host, pathogen, vector, virulence, vaccine, transmission – accompanied by IDO Extensions for specific diseases, pathogens and vectors Provides common terminology resources and tested common guidelines for a vast array of different disease communities 110
  • 91. Infectious Disease Ontology Consortium • MITRE, Mount Sinai, UTSouthwestern – Influenza • IMBB/VectorBase – Vector borne diseases (A. gambiae, A. aegypti, I. scapularis, C. pipiens, P. humanus) • Colorado State University – Dengue Fever • Duke University – Tuberculosis, Staph. aureus • Cleveland Clinic – Infective Endocarditis • University of Michigan – Brucellosis • Duke University, University at Buffalo – HIV 111
  • 92. Influenza - infectious• Etiological process - infection of airway epithelial cells with influenza virus – produces• Disorder - viable cells with influenza virus – bears• Disposition (disease) - flu – realized_in• Pathological process - acute inflammation – produces• Abnormal bodily features – recognized_as• Symptoms - weakness, dizziness• Signs - fever 112
  • 93. Influenza – disease course• Etiological process - infection of airway epithelial cells with influenza virus – produces• Disorder - viable cells with influenza virus – bears• Disposition (disease) - flu – realized_in• Pathological process - The disorder also induces normal acute inflammation – produces physiological processes (immune• Abnormal bodily featuresresponse) that can results in the – recognized_as elimination of the disorder (transient• Symptoms - weakness, dizziness disease course).• Signs - fever 113
  • 94. Big Picture 114