2
genomic medicine, molecular medicine, translational medicine, personalized medicine ...
need
methods for data integration to enable reasoning across data at multiple granularities
to identify biomedically relevant relations on the side of the entities themselves
4
where in the body ?
what kind of disease process ?
we need semantic annotations of data which human beings can understand
and computers can reason with
6
Institute for Formal Ontology and Medical Information Science (IFOMIS) Institute for Formal Ontology and Medical Information Science (IFOMIS) Institute for Formal Ontology and Medical Information Science (IFOMIS)
BIRN: Bioinformatics Research Network
7
Institute for Formal Ontology and Medical Information Science (IFOMIS) Institute for Formal Ontology and Medical Information Science (IFOMIS) Institute for Formal Ontology and Medical Information Science (IFOMIS)
BIRN: Bioinformatics Research Network
Center for In Vivo Microscopy
Brain Imaging and Analysis Center
Neuropsychiatric Imaging Research Laboratory
Yerkes National Primate Research Center
Clinical Cognitive Neuroscience Laboratory
Mallinkrodt Institute of Radiology
Lineberger Comprehensive Cancer Center
fMRI Research Center
Surgical Planning Laboratory
Center for Magnetic Resonance Research
Multiscale Systems Immunology for Adjuvant [Vaccine] Development
Investigators
Duke Center for Computional ImmunologyThomas B KeplerLindsay G CowellCliburn Chan
Duke Center for Computational Sciences, Engineering and MedicineJohn PormannRachael BradyBill Rankin
Duke MathematicsBill Allard
Duke Institute of Statistics and Decision SciencesMike West
Duke Computer ScienceJun Yang
Duke Human Vaccine InstituteGreg SempowskiMunir Alam
Department of Pathology,EmoryBali Pulendran
Department of Physiology & Biophysics, UC IrvineMichael Cahalan
Department of Pediatrics, Vanderbilt Kathryn Edwards
9
how do we make different sorts of data combinable in ways useful to the human beings who carry out research?
10
how was this problem solved in the years BC?
how did clinical researchers from different disciplines communicate?
how did they learn to communicate?
12
create ontologies corresponding to the basic biomedical sciences
clinical medicine relies on anatomy
and molecular biology to provide
integration across medical specialisms
14
where do we find scientifically validated information linking gene products and other entities represented in biochemical databases to semantically meaningful terms pertaining to disease, anatomy, development, histology in different model organisms?
but we need more
17
different model organism databases employ scientific curators who use the experimental observations reported in the biomedical literature to associate GO terms with gene products in a coordinated way
The methodology of annotations:
18
cellular locations
molecular functions
biological processes
used to annotate the entities represented in the major biochemical databases
thereby creating integration across these databases and making them available to semantic search
A set of standardized textual descriptions of
20
This process
leads to a slowly growing computer-interpretable map of biological reality within which major databases are automatically integrated in semantically searchable form
21
Five bangs for your GO buckscience base
cross-species database integration
cross-granularity database integration
through links to the things which are of biomedical relevance
semantic searchability links people to software
22
but alsoneed to extend this methodology beyond the basic biomedical sciences, to clinical domains
disease ontology
immunology ontology
symptom (phenotype) ontology
neuron ontology
brain (mal)function ontology ...
23
the problem
need to ensure consistency of the new clinical ontologies with the basic biomedical sciences
need to find ways to ensure clinical data is annotated in terms of these new controlled vocabularies
if we do not start now, the problem will only get worse
24
a shared portal for (so far) 58 ontologies (low regimentation)
http://obo.sourceforge.net NCBO BioPortal
First step (2003)First step (2003)
26
Second step (2004)Second step (2004)reform efforts initiated, e.g. linking GO to other
OBO ontologies to ensure orthogonality
id: CL:0000062name: osteoblastdef: "A bone-forming cell which secretes an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone." is_a: CL:0000055relationship: develops_from CL:0000008relationship: develops_from CL:0000375
GO
Cell type
New Definition
+
=Osteoblast differentiation: Processes whereby an osteoprogenitor cell or a cranial neural crest cell acquires the specialized features of an osteoblast, a bone-forming cell which secretes extracellular matrix.
27
The OBO FoundryThe OBO Foundryhttp://obofoundry.org/http://obofoundry.org/
Third step (2006)Third step (2006)
28
a family of interoperable gold standard biomedical reference ontologies to serve the annotation of inter alia
scientific literature
model organism databases
clinical trial data
The OBO FoundryThe OBO Foundry
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
29
A prospective standarddesigned to guarantee interoperability of ontologies from the very start (contrast to: post hoc mapping)
established March 2006
12 initial candidate OBO ontologies – focused primarily on basic science domains
several being constructed ab initio
by influential consortia who have the authority to impose their use on large parts of the relevant communities.
30
undergoing rigorous reform
new
GO Gene OntologyChEBI Chemical Ontology CL Cell OntologyFMA Foundational Model of AnatomyPaTO Phenotype Quality OntologySO Sequence Ontology
CARO Common Anatomy Reference Ontology CTO Clinical Trial OntologyFuGO Functional Genomics Investigation OntologyPrO Protein Ontology RnaO RNA Ontology RO Relation Ontology
31
already in good shape
GO Gene OntologyChEBI Chemical Ontology CL Cell OntologyFMA Foundational Model of AnatomyPaTO Phenotype Quality OntologySO Sequence Ontology
CARO Common Anatomy Reference Ontology CTO Clinical Trial OntologyFuGO Functional Genomics Investigation OntologyPrO Protein Ontology RnaO RNA Ontology RO Relation Ontology
Pleural Cavity
Pleural Cavity
Interlobar recess
Interlobar recess
Mesothelium of Pleura
Mesothelium of Pleura
Pleura(Wall of Sac)
Pleura(Wall of Sac)
VisceralPleura
VisceralPleura
Pleural SacPleural Sac
Parietal Pleura
Parietal Pleura
Anatomical SpaceAnatomical Space
OrganCavityOrganCavity
Serous SacCavity
Serous SacCavity
AnatomicalStructure
AnatomicalStructure
OrganOrgan
Serous SacSerous Sac
MediastinalPleura
MediastinalPleura
TissueTissue
Organ PartOrgan Part
Organ Subdivision
Organ Subdivision
Organ Component
Organ Component
Organ CavitySubdivision
Organ CavitySubdivision
Serous SacCavity
Subdivision
Serous SacCavity
Subdivision
part
_of
is_a
Foundational Model of Anatomy
33
RELATION TO TIME
GRANULARITY
CONTINUANT OCCURRENT
INDEPENDENT DEPENDENT
ORGAN ANDORGANISM
Organism(NCBI
Taxonomy?)
Anatomical Entity
(FMA, CARO)
OrganFunction
(FMP, CPRO) Phenotypic
Quality(PaTO)
Organism-Level Process
(GO)
CELL AND CELLULAR
COMPONENT
Cell(CL)
Cellular Compone
nt(FMA, GO)
Cellular Function
(GO)
Cellular Process
(GO)
MOLECULEMolecule
(ChEBI, SO,RnaO, PrO)
Molecular Function(GO)
Molecular Process
(GO)
34
RELATION TO TIME
GRANULARITY
CONTINUANT OCCURRENT
INDEPENDENT DEPENDENT
ORGAN ANDORGANISM
Organism(NCBI
Taxonomy?)
Anatomical Entity
(FMA, CARO)
OrganFunction
(FMP, CPRO) Phenotypic
Quality(PaTO)
Biological Process
(GO)CELL AND CELLULAR
COMPONENT
Cell(CL)
Cellular Compone
nt(FMA, GO)
Cellular Function
(GO)
MOLECULE Molecule
(ChEBI, SO,RnaO, PrO)
Molecular Function(GO)
Molecular Process
(GO)
Building out from the original GO
35
Disease Ontology (DO)
Biomedical Image Ontology (BIO)
Upper Biomedical Ontology (OBO UBO)
Environment Ontology (EnvO)
Systems Biology Ontology (SBO)
Under consideration:
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
36
OBO Foundry = a subset of OBO ontologies, whose developers have agreed in advance to accept a common set of principles reflecting best practice in ontology development designed to ensure
tight connection to the biomedical basic sciences
compatibility
interoperability, common relations
formal robustness
support for logic-based reasoning
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
37
CRITERIA The ontology is OPEN
The ontology employs a COMMON FORMAL LANGUAGE.
The developers agree to COLLABORATE
UPDATE in light of scientific advance
ORTHOGONALITY: one ontology per domain
38
COMMON ARCHITECTURE: The ontology uses relations which are unambiguously defined following the pattern of definitions laid down in the OBO Relation Ontology.*
* Smith et al., Genome Biology 2005, 6:R46
CRITERIA
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
39
Further criteria will be added over time in light of lessons learned in order to bring about a gradual improvement in the quality of Foundry ontologies
ALL FOUNDRY ONTOLOGIES WILL BE SUBJECT TO CONSTANT UPDATE IN LIGHT OF SCIENTIFIC ADVANCE
IT WILL GET HARDER
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
40
But not everyone needs to join
The Foundry is not seeking to serve as a check on flexibility or creativity
ALL FOUNDRY ONTOLOGIES WILL ENCOURAGE COMMUNITY CRITICISM, CORRECTION AND EXTENSION WITH NEW TERMS
IT WILL GET HARDER
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
41
to introduce some of the features of SCIENTIFIC PEER REVIEW into biomedical ontology development
KUDOS for early adopters of high quality ontologies / terminologies e.g. in reporting clinical trial results
establish ONTOLOGY CHAMPIONS to create EVIDENCE-BASED TERMINOLOGY RESEARCH
GOALS
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
42
DATA REUSABILITY: if data-schemas are formulated using a single well-integrated framework ontology system in widespread use, then this data will be to this degree itself become more widely accessible and usable
GOALS
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
43
June 2006: establishment of MICheck:
reflects growing need for prescriptive checklists specifying the key information to include when reporting experimental results (concerning methods, data, analyses and results).
expand to all areas of biomedical experimentation
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
44
MICheck: ‘a common resource for minimum information checklists’ analogous to OBO / NCBO BioPortal
MICheck Foundry: will create ‘a suite of self-consistent, clearly bounded, orthogonal, integrable checklist modules’ *
* Taylor CF, et al. Nature Biotech, in press
MICheck Foundry
The OBO FoundryThe OBO Foundry http://obofoundry.org/http://obofoundry.org/
45
Transcriptomics (MIAME Working Group)
Proteomics (Proteomics Standards Initiative)
Metabolomics (Metabolomics Standards Initiative)
Genomics and Metagenomics (Genomic Standards Consortium)
In Situ Hybridization and Immunohistochemistry (MISFISHIE Working Group)
Phylogenetics (Phylogenetics Community)
RNA Interference (RNAi Community)
Toxicogenomics (Toxicogenomics WG)
Environmental Genomics (Environmental Genomics WG)
Nutrigenomics (Nutrigenomics WG)
Flow Cytometry (Flow Cytometry Community)
MICheck/Foundry communities
46
how to replicate the successes of the GO in clinical medicine:
choose two or three representative disease domains
work out reasoning challenges for those domains
work with specialists to create ontologies interoperable with OBO Foundry basic science ontologies to address these reasoning challenges
work with leaders of clinical trial initiatives to foster the collection of clinical data annotated in their terms
Fourth Step (the future)Fourth Step (the future)
Draft Ontology for Muscular Sclerosis
what data do we have?
what data do the others have?
what data do we not have?
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