Ontology in Buffalo September 29, 2014 Barry Smith

Stanford University Biomedical Informatics Research Mayo Clinic Department of Biomedical Informatics University at Buffalo Department of Philosophy Three US partner institutions:

RELATION TO TIME GRANULARITY CONTINUANTOCCURRENT INDEPENDENTDEPENDENT ORGAN AND ORGANISM Organism (NCBI Taxonomy) Anatomical Entity (FMA, CARO) Organ Function (FMP, CPRO) Phenotypic Quality (PaTO) Biological Process (GO) CELL AND CELLULAR COMPONENT Cell (CL) Cellular Component (FMA, GO) Cellular Function (GO) MOLECULE Molecule (ChEBI, SO, RnaO, PrO) Molecular Function (GO) Molecular Process (GO) Open Biomedical Ontologies (OBO) Foundry (Gene Ontology marked in yellow)

© Ocean Informatics Enterprise Comprehensive Basic Components EHR Multimedia genetics workflow identity Clinical ref data Clinical models terms Security / access control realtime gateway telemedicine HILS other provider UPDATE QUERY demographics guidelines protocols Interactions DS Local modelling notifications DSSPAS billing portal Allied health patient PAYER Msg gateway Imaging lab ECG etc Path lab LAB Secondary users Online drug, Interactions DB Online archetypes Online terminology Online Demographic registries Patient Record

Grants IDO: Immune System Biological Networks: A Case Study in Improved Data Integration & Analysis (NIH / NIAID) ImmPort: Bioinformatics Integration Support Contract (NIH/NIAID) Plant Ontology (NSF) OPMQoL: Ontology for Pain and Related Disability, Mental Health and Quality of Life (NIH/National Institute of Dental and Craniofacial Research) PRO: A Protein Ontology in Open Biomedical Ontologies (NIH/NIGMS) NCBO: National Center for Biomedical Ontology (NIH/NHGRI)

Military Ontology

11

Explosion of “biomedical ontology” since 1999

Biomedical Ontology in Buffalo

BS, Alan Ruttenberg, Alex Diehl Philosophy Dental School, IHI Neurology

Werner Ceusters, Dagobert Soergel, Peter Elkin Psychiatry, IHI Dental School, Library and Information Studies Biomedical Informatics

IHI: Institute for Healthcare Informatics

Peter Winkelstein

IHI Ontology Machine

Biomedical Ontologies co-developed at UB BCOBiocollections Ontology BFOBasic Formal Ontology CLCell Ontology ENVOEnvironment Ontology FMAFoundational Model of Anatomy GOGene Ontology IDOInfectious Disease Ontology NDNeurological Disease Ontology MFOMental Functioning Ontology NPTNeuropsychological Testing Ontology OBIOntology for Biomedical Investigations OGMSOntology for General Medical Science OHDOral Health and Disease Ontology PCOPopulation and Community Ontology POPlant Ontology PROProtein Ontology

Biomedical Ontologies co-developed at UB BCOBiocollections Ontology BFOBasic Formal Ontology CLCell Ontology ENVOEnvironment Ontology FMAFoundational Model of Anatomy GOGene Ontology IDOInfectious Disease Ontology NDNeurological Disease Ontology MFOMental Functioning Ontology NPTNeuropsychological Testing Ontology OBIOntology for Biomedical Investigations OGMSOntology for General Medical Science OHDOral Health and Disease Ontology PCOPopulation and Community Ontology POPlant Ontology PROProtein Ontology

Biomedical Ontologies co-developed at UB BCOBiocollections Ontology BFOBasic Formal Ontology CLCell Ontology ENVOEnvironment Ontology FMAFoundational Model of Anatomy GOGene Ontology IAOInformation Artifact Ontology IDOInfectious Disease Ontology NDNeurological Disease Ontology MFOMental Functioning Ontology NPTNeuropsychological Testing Ontology OBIOntology for Biomedical Investigations OGMSOntology for General Medical Science PCOPopulation and Community Ontology POPlant Ontology PROProtein Ontology

OGMS Big Picture 24

From BFO to OGMS Material Entity Disposition Process Disorder Disease Disease Course BFO

Top-level terms in the OGMS ontology Disorder = part of an organism which deviates from the normal (a necrotic liver …) Disease = a disposition to bad things which exists in virtue of one or more disorders Disease course = the realization (manifestation) of such a disposition

OGMS Big Picture 27

Huntington’s Disease - genetic Etiological process - inheritance of >39 CAG repeats in the HTT gene – produces Disorder - chromosome 4 with abnormal mHTT – bears Disposition (disease) - Huntington’s disease – realized_in Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum – produces Abnormal bodily features – recognized_as Symptoms - anxiety, depression Signs - difficulties in speaking and swallowing

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

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 Pre-disposition = A disposition to acquire a disposition

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

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, splenomegaly

Systemic arterial hypertension Etiological process – abnormal reabsorption of NaCl by the kidney – produces Disorder – abnormally large scattered molecular aggregate of salt in the blood – bears Disposition (disease) - hypertension – realized_in Pathological process – exertion of abnormal pressure against arterial wall – produces Abnormal bodily features – recognized_as Signs – elevated blood pressure

Type 2 Diabetes Mellitus Etiological process – – produces Disorder – abnormal pancreatic beta cells or abnormal muscle/fat cells – bears Disposition (disease) – diabetes mellitus – realized_in Pathological processes – diminished insulin production, diminished muscle/fat uptake of glucose – produces Abnormal bodily features – recognized_as Symptoms – polydipsia, polyuria, polyphagia, blurred vision Signs – elevated blood glucose and hemoglobin A1c

Type 1 hypersensitivity to penicillin Etiological process – sensitizing of mast cells and basophils during exposure to penicillin-class substance – produces Disorder – mast cells and basophils with epitope-specific IgE bound to Fc epsilon receptor I – bears Disposition (disease) – type I hypersensitivity – realized_in Pathological process – type I hypersensitivity reaction – produces Abnormal bodily features – recognized_as Symptoms – pruritis, shortness of breath Signs – rash, urticaria, anaphylaxis

Huntington’s Disease - genetic Etiological process - inheritance of >39 CAG repeats in the HTT gene – produces Disorder - chromosome 4 with abnormal mHTT – bears Disposition (disease) - Huntington’s disease – realized_in Pathological process - accumulation of mHTT protein fragments, abnormal transcription regulation, neuronal cell death in striatum – produces Abnormal bodily features – recognized_as Symptoms - anxiety, depression Signs - difficulties in speaking and swallowing Symptoms & Signs used_in Interpretive process produces Hypothesis - rule out Huntington’s suggests Laboratory tests produces Test results - molecular detection of the HTT gene with >39CAG repeats used_in Interpretive process produces Result - diagnosis that patient X has a disorder that bears the disease Huntington’s disease Information Artifacts

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

Biomedical Ontologies co-developed at UB BCOBiocollections Ontology CLCell Ontology ENVOEnvironment Ontology FMAFoundational Model of Anatomy GOGene Ontology IDOInfectious Disease Ontology NDNeurological Disease Ontology MFOMental Functioning Ontology NPTNeuropsychological Testing Ontology OBIOntology for Biomedical Investigations OGMSOntology for General Medical Science PCOPopulation and Community Ontology POPlant Ontology PROProtein Ontology

From OGMS to IDO Core Disorder Disease Disease Course Infection Infectious Disease Infectious Disease Course

Core and Extensions IDOInfectious Disease Ontology IDO-BRUBrucellosis Ontology IDO-HIVHIV Ontology IDO-FLUInfluenza Ontology IDO-DENGUEDengue Ontology IDO-STAPHStaph. Aureus Ontology IDO-PLANTPlant Infectious Disease Ontology IDO-MRSAMethicillin-Resistant Staph. Aureus Ontology IDO-VectorVector-Borne Infectious Disease Ontology IDO-MALMalaria Ontology

Core and Extensions IDO CoreInfectious Disease Ontology IDO-BRUBrucellosis Ontology IDO-HIVHIV Ontology IDO-DENGUE IDO-STAPHStaph. aureus Ontology IDO-MRSAMethicillin-Resistant Staph. aureus Ontology IDO-VectorborneVector-Borne Infectious Disease Ontology IDO-MALMalaria Ontology IDO-PLANT

From IDO Core to IDO STAPH Sa Infection Sa Bacteremia Sa Bacteremia Disease Course Infection Infectious Disease Infectious Disease Course

From BFO to IDO Core to IDO STAPH IDOCore IDO STAPH OGMS IDOHIV IDOFLU BFO

IDO STAPH and its Extensions IDOCore IDO STAPH IDOHumanSa IDORatSa IDOStrep IDORatStrep IDOHumanStrep IDOMRSa IDOHumanBacterial IDOAntibioticResistant IDOMALIDOHIV IDOFLU

How we ensure consistent data as new Staph. aureus strains evolve IDOCore IDO STAPH IDOHumanSa IDORatSa IDOStrep IDORatStrep IDOHumanStrep IDOMRSa IDOHumanBacterial IDOAntibioticResistant IDOMALIDOHIV IDOFLU

IHI using BFO, OGMS and their extension ontologies to provide a consistent framework for the representation of the types of particulars developing systematic ways for the consistent tracking of particulars (patients, disorders, encounters …) putting these together to serve consistent representation of the assertional knowledge in the IHI repository