Difference between revisions of "DallasWorkshop"
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''Workshop organized by:'' | ''Workshop organized by:'' | ||
− | + | ||
− | + | [http://www.utsouthwestern.edu/findfac/research/0,2357,16416,00.html Richard Scheuermann], University of Texas Southwestern Medical Center, Dallas | |
+ | |||
+ | [http://ontology.buffalo.edu/smith/ Barry Smith], National Center for Biomedical Ontology / University at Buffalo | ||
+ | |||
+ | |||
''Sponsored by:'' | ''Sponsored by:'' | ||
− | + | ||
− | + | [http://www.utsouthwestern.edu/utsw/home/home/research/ctsa University of Texas Southwestern Medical Center Clinical and Translational Science Award (CTSA) Program] | |
+ | |||
+ | [http://www.bioontology.org/ National Center for Biomedical Ontology (NCBO)] | ||
+ | |||
+ | [http://www.leadhorsetech.com/LEAD_HORSE_TECHNOLOGIES/Home.html Lead Horse Technologies, Inc.] | ||
+ | |||
+ | |||
''Date:'' | ''Date:'' | ||
− | + | ||
+ | September 3-4, 2008 | ||
+ | |||
+ | |||
''Venue:'' | ''Venue:'' | ||
− | + | ||
− | + | Dallas/Fort Worth Airport Marriott [http://www.marriott.com/hotels/travel/dfwap-dallas-fort-worth-airport-marriott/]. | |
− | + | *To take advantage of discounted rate at the conference hotel, guest room reservations must be secured '''no later than August 15'''. See Workshop registration form for further details. | |
+ | *There is no participation fee. Continental breakfast and refreshments will be provided to all registered participants at no cost. | ||
This workshop is funded by the United States National Institutes of Health (NIH) through the NIH Roadmap for Medical Research, Grant 1 U54 HG004028, with support from the Clinical and Translational Science Award (1 U54 RR023468) and the Bioinformatics Integration Support Contract (1 N01 AI40076). | This workshop is funded by the United States National Institutes of Health (NIH) through the NIH Roadmap for Medical Research, Grant 1 U54 HG004028, with support from the Clinical and Translational Science Award (1 U54 RR023468) and the Bioinformatics Integration Support Contract (1 N01 AI40076). | ||
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==Overview== | ==Overview== | ||
− | The aims of clinical and translational research are to achieve a better understanding of the pathogenesis of human disease in order to develop effective diagnostic, therapeutic and prevention strategies. Biomedical informatics can play an important role | + | The aims of clinical and translational research are to achieve a better understanding of the pathogenesis of human disease in order to develop effective diagnostic, therapeutic and prevention strategies. Biomedical informatics can play an important role in supporting this research by facilitating the management, integration, analysis and exchange of data derived from and related to the research problems being studied. A key aspect of this support is to bring clarity, rigor and formalism to the representation of |
::1. disease initiation, progression, pathogenesis, signs, symptoms, assessments, clinical and laboratory findings, disease diagnosis, treatment, treatment response and outcome, and | ::1. disease initiation, progression, pathogenesis, signs, symptoms, assessments, clinical and laboratory findings, disease diagnosis, treatment, treatment response and outcome, and | ||
Line 34: | Line 48: | ||
==Goals== | ==Goals== | ||
− | The | + | The goals of the workshop are: |
+ | |||
+ | *to utilize consistent ontological design and development principles to describe disease signs and symptoms, clinical and laboratory findings, and their interrelations. | ||
+ | |||
+ | *to delineate the roles that signs, symptoms and findings play in both clinical patient management and in clinical research. | ||
+ | |||
+ | *to develop a clear understanding and representation of the distinction between clinical and pre-clinical manifestations of signs, symptoms and findings. | ||
+ | |||
+ | *to take first steps towards harmonizing the ontological representation of disease signs and symptoms and clinical and laboratory findings with existing and emerging standards in knowledge representation from the health informatics and bioinformatics communities | ||
+ | |||
+ | *to explore incorporation of the results of this work into the CTSA Human Studies Metadata Repository framework | ||
− | + | ==Agenda== | |
− | + | '''Day 1: Wednesday, September 3''' (Room: Irving I-III, Lobby Level) | |
− | + | 8:30am - Registration and Continental Breakfast | |
− | + | 9:00am - Opening remarks / Workshop goals (Richard Scheuermann) | |
− | + | 9:15am - Session 1: Signs, symptoms and laboratory findings from a health care perspective (Scheuermann, moderator) | |
− | + | ::: Combining clinical exam and laboratory findings in the rheumatology clinic [http://ontology.buffalo.edu/08/phenotype/karp.ppt slides] (David Karp) | |
+ | ::: Clinical signs and findings in neonatology [http://ontology.buffalo.edu/08/phenotype/JAMES.ppt slides] (Andrew James) | ||
− | + | 10:30am - Refreshment Break | |
− | + | 10:45am - Session 2: Ontology approaches to describing the clinical phenotype [http://ontology.buffalo.edu/08/phenotype/SMITH.ppt slides] (Smith, moderator) | |
− | + | ::: Reasoning with clinical exam and laboratory findings: The case of myocardial infarction [http://ontology.buffalo.edu/08/phenotype/ARABANDI.pdf slides] (Sivaram Arabandi) | |
− | : | + | 12:00pm - Buffet Lunch (Arlington Room, Lower Level), '''''Provided by the generous support of''''' [http://www.leadhorsetech.com/LEAD_HORSE_TECHNOLOGIES/Home.html '''''Lead Horse Technologies, Inc.'''''] |
− | + | 1:00pm - Session 3: Standardization of clinical and laboratory data in the context of clinical and translational research (Jaffe, moderator) | |
− | :: | + | ::: Data standards from patient care to clinical and translational research: The CTSA perspective [http://ontology.buffalo.edu/08/phenotype/CHUTE.ppt slides] (Chris Chute) |
− | :: | + | ::: Representation of clinical and laboratory findings in the CDISC SDTM [http://ontology.buffalo.edu/08/phenotype/KISLER-WALKER.ppt slides] (Bron Kisler and Gary Walker) |
− | :: | ||
− | + | 3:00pm - Refreshment Break | |
− | + | 3:30pm - Session 3 continued (Ruttenberg, moderator) | |
− | :: | + | ::: The future of SNOMED-CT in the representation of clinical findings [http://ontology.buffalo.edu/08/phenotype/SPACKMAN.ppt slides] (Kent Spackman) |
− | : | + | ::: Problems with current approaches to clinical data [http://ontology.buffalo.edu/08/phenotype/HOGAN.ppt slides] (William Hogan) |
− | |||
− | :: | ||
− | ''' | + | 5:30pm - Reception (Grand Prairie Room, Lower Level), '''''Provided by the generous support of The Cleveland Clinic Foundation SemanticDB''''' |
− | |||
− | + | '''Day 2: Thursday, September 4''' (Room: Irving I-III, Lobby Level) | |
− | : | + | 8:30am - Continental Breakfast |
− | |||
− | + | 9:00am - Session 4: Proposals for unification of standard terminologies for the representation ‘sign’, ‘symptom’, ‘finding’ and related terms (Lewis, moderator) | |
− | + | ::: Laboratory data and metadata in laboratory information systems [http://ontology.buffalo.edu/08/phenotype/BURGUN.ppt slides] (Anita Burgun) | |
+ | ::: An ontology-based approach for connecting disease pathogenesis with clinical/laboratory data [http://ontology.buffalo.edu/08/phenotype/SCHEUERMANN.ppt slides] (Richard Scheuermann) | ||
− | + | 10:30am - Refreshment Break | |
− | + | 10:45am - Session 5: How consistent ontological design and development principles can lead to enhanced representation of signs, symptoms, and clinical and laboratory finding (Smith, moderator) | |
+ | ::: PATO and Phenote: From model organism phenotypes to clinical medicine [http://ontology.buffalo.edu/08/phenotype/LEWIS.ppt slides] (Suzanna Lewis) | ||
− | + | 12:00pm - Lunch Break | |
− | + | 1:00pm - Session 6: Strategies to achieve convergence of ontologies, vocabularies and data structures in representing signs, symptoms, and clinical and laboratory findings (Scheuermann, moderator) | |
− | ( | + | 2:30pm - Refreshment Break |
− | *Jonas Silva Almeida ( | + | |
− | *Sivaram Arabandi (Cleveland Clinic | + | 2:45pm - Session 6 (continued) |
− | *Robert Arp (National Center for Biomedical Ontology / University at Buffalo | + | |
− | + | 4:00pm - Close | |
− | *Elmer V. Bernstam (University of Texas Health Science Center at Houston) | + | |
− | * | + | ==Summary of Workshop== |
− | *Anita Burgun (Université de Rennes | + | |
− | + | * Summary [http://esw.w3.org/topic/HCLSIG/Meetings/2008-10-02_Conference_Call?action=AttachFile&do=get&target=NCBO_clinical_phenotype_ont.pdf slides] (Kei Cheung) | |
− | *Kei Cheung (Senselab / Yale | + | |
− | *Christopher Chute ( | + | ==Participants== |
− | *Paolo Ciccarese (Mass General Hospital / Harvard Medical School) | + | |
− | *Timothy W. Clark (Mass General Institute for Neurodegenerative Disease / Harvard Medical School) | + | [[image:photo.jpg|thumb|right]] |
− | *Gianluca Colombo (University of Milano-Bicocca, DISCo) | + | |
− | *Amar K. Das ( | + | *Jonas Silva Almeida (MD Anderson Cancer Center / University of Texas) |
− | *Louis J. Goldberg (Ontology Research Group / University at Buffalo | + | *Sivaram Arabandi (Heart & Vascular Institute / Cleveland Clinic) |
− | + | *John M. Armstrong (Lead Horse Technologies, Inc.) | |
− | *Herb Hagler (University of Texas Southwestern Medical Center at Dallas | + | *Robert Arp (National Center for Biomedical Ontology / University at Buffalo) |
− | + | *Elmer V. Bernstam (University of Texas Health Science Center at Houston) | |
− | *William Hogan (University of Pittsburgh Medical Center) | + | *Bruce Bray (Dept of Biomedical Informatics, University of Utah) |
− | *Zhang- | + | *Anita Burgun (Université de Rennes) |
− | *Charles Jaffe (HL7) | + | *Kei-Hoi Cheung (Senselab / Yale Center for Medical Informatics) |
− | *Andrew G. James (Division of Neonatology, The Hospital for Sick Children / University of Toronto) | + | *Christopher G. Chute (National Center for Biomedical Ontology / Mayo Clinic) |
− | *David Karp (University of Texas Southwestern Medical Center at Dallas) | + | *Paolo Ciccarese (Mass General Hospital / Harvard Medical School) |
− | *Bron Kisler (CDISC) | + | *Timothy W. Clark (Mass General Institute for Neurodegenerative Disease / Harvard Medical School) |
+ | *Gianluca Colombo (University of Milano-Bicocca, DISCo) | ||
+ | *Tommie G. Curtis (SAIC, NCICB Contractor) | ||
+ | *Amar K. Das (Center for Biomedical Informatics Research / Stanford University) | ||
+ | *Louis J. Goldberg (Ontology Research Group / University at Buffalo) | ||
+ | *Herb Hagler (University of Texas Southwestern Medical Center at Dallas) | ||
+ | *William Hogan (University of Pittsburgh Medical Center) | ||
+ | *Zhang-Zhi Hu (PRO / Georgetown University Medical Center) | ||
+ | *Charles Jaffe (Health Level 7, Inc. (HL7)) | ||
+ | *Andrew G. James (Division of Neonatology, The Hospital for Sick Children / University of Toronto) | ||
+ | *David Karp (University of Texas Southwestern Medical Center at Dallas) | ||
+ | *Bron Kisler (CDISC) | ||
+ | *Megan Kong (University of Texas Southwestern Medical Center at Dallas) | ||
*Suzanna Lewis (Lawrence Berkeley National Laboratory) | *Suzanna Lewis (Lawrence Berkeley National Laboratory) | ||
− | *Daniele Merico (NEUROWEB / University of Toronto & University of Milano-Bicocca, DISCo) | + | *Daniele Merico (NEUROWEB / University of Toronto & University of Milano-Bicocca, DISCo) |
− | * | + | *Pradeep Mutalik (Yale Center for Medical Informatics) |
− | *Chimezie Ogbuji (Cleveland Clinic | + | *Chimezie Ogbuji (Cleveland Clinic Foundation) |
− | + | *John Quinn (Health Level 7, Inc. (HL7)) | |
− | *John Quinn (HL7) | + | *Alan Ruttenberg (Science Commons / Neurocommons) |
− | *Alan Ruttenberg (Science Commons / Neurocommons) | + | *Neil Sarkar (Marine Biological Laboratory) |
− | *Neil Sarkar (Marine Biological Laboratory | + | *Richard Scheuermann (University of Texas Southwestern Medical Center at Dallas) |
− | *Richard Scheuermann (University of Texas Southwestern Medical Center at Dallas) | + | *Lynn M. Schriml (Institute for Genome Sciences, University of Maryland) |
− | *Lynn M. Schriml (Institute for Genome Sciences, University of Maryland) | + | *Barry Smith (National Center for Biomedical Ontology / University at Buffalo) |
− | *Barry Smith (National Center for Biomedical Ontology / University at Buffalo) | + | *Kent A. Spackman (International Health Terminology Standards Development Organization) |
− | *Kent A. Spackman (International Health Terminology Standards Development Organization) | + | *Larry Streepy (Cleveland Clinic Foundation) |
− | * | + | *Gary Walker (Quintiles) |
− | *Ashley Xia (NIAID / NIH) | + | *Ashley Xia (NIAID / NIH) |
− | *W. Jim Zheng (Biomedical Ontology Research Group | + | *W. Jim Zheng (Biomedical Ontology Research Group / Medical University of South Carolina) |
− | In addition to NCBO and the University of Texas Southwestern Medical Center, | + | In addition to NCBO and the University of Texas Southwestern Medical Center, the following communities are represented: CTSA, HL7, CDISC, OBO, SNOMED, and the NIH. |
==Suggested Background Reading== | ==Suggested Background Reading== | ||
+ | |||
+ | [http://ontology.buffalo.edu/medo/continua.pdf Continua in Biological Systems], Stefan Schulz and Ingvar Johansson, The Monist, 2007; 90(4), 499-522. | ||
[http://nuke.neurowebkc.eu/LinkClick.aspx?fileticket=opFTkenwCz0%3D&tabid=66&mid=435 NEUROWEB Project]: From Clinically-Based Phenotypes to Genomics Integration | [http://nuke.neurowebkc.eu/LinkClick.aspx?fileticket=opFTkenwCz0%3D&tabid=66&mid=435 NEUROWEB Project]: From Clinically-Based Phenotypes to Genomics Integration | ||
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[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1781118 PhenomicDB]: A New Cross-Species Genotype/Phenotype Resource | [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1781118 PhenomicDB]: A New Cross-Species Genotype/Phenotype Resource | ||
+ | |||
+ | [http://org.buffalo.edu/RTU/papers/WhatIsaDiagnosis.ppt What is a Diagnosis?], Werner Ceusters | ||
+ | |||
+ | [http://bmir.stanford.edu/file_asset/index.php/1338/BMIR-2008-1302.pdf Using an Integrated Ontology and Information Model for Querying and Reasoning about Phenotypes: The Case of Autism], Samson W. Tu, Lakshika Tennakoon, Martin O'Connor, Ravi Shankar, and Amar Das. | ||
+ | |||
+ | [http://ontology.buffalo.edu/medo/Williams_Disease.pdf The Factory Model of Disease], Neil Williams, The Monist, 2007; 90(4): 555-584. | ||
+ | |||
+ | [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1948102 Human disease classification in the postgenomic era], J. Loscalzo, I. Kohane and A.-L. Barabasi | ||
==Useful Links== | ==Useful Links== | ||
Line 154: | Line 198: | ||
[http://www.bioontology.org/wiki/index.php/PATO:Main_Page Phenotypic Quality Ontology] | [http://www.bioontology.org/wiki/index.php/PATO:Main_Page Phenotypic Quality Ontology] | ||
+ | |||
+ | ==Proposed Terms and Definitions== | ||
+ | |||
+ | * [[Clinical Phenotypes | Toward an Ontological Treatment of the Initiation, Realization, Recognition, and Representation of Disease]] | ||
+ | |||
+ | ==Follow-Up Meeting 2009== | ||
+ | |||
+ | [http://bimib.disco.unimib.it/index.php/SSFW09 Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes] |
Latest revision as of 07:44, 7 April 2009
Signs, Symptoms and Findings: First Steps Toward an Ontology of Clinical Phenotypes
Workshop organized by:
Richard Scheuermann, University of Texas Southwestern Medical Center, Dallas
Barry Smith, National Center for Biomedical Ontology / University at Buffalo
Sponsored by:
National Center for Biomedical Ontology (NCBO)
Date:
September 3-4, 2008
Venue:
Dallas/Fort Worth Airport Marriott [1].
- To take advantage of discounted rate at the conference hotel, guest room reservations must be secured no later than August 15. See Workshop registration form for further details.
- There is no participation fee. Continental breakfast and refreshments will be provided to all registered participants at no cost.
This workshop is funded by the United States National Institutes of Health (NIH) through the NIH Roadmap for Medical Research, Grant 1 U54 HG004028, with support from the Clinical and Translational Science Award (1 U54 RR023468) and the Bioinformatics Integration Support Contract (1 N01 AI40076).
Information on the National Centers for Biomedical Computing can be found at: [2].
Overview
The aims of clinical and translational research are to achieve a better understanding of the pathogenesis of human disease in order to develop effective diagnostic, therapeutic and prevention strategies. Biomedical informatics can play an important role in supporting this research by facilitating the management, integration, analysis and exchange of data derived from and related to the research problems being studied. A key aspect of this support is to bring clarity, rigor and formalism to the representation of
- 1. disease initiation, progression, pathogenesis, signs, symptoms, assessments, clinical and laboratory findings, disease diagnosis, treatment, treatment response and outcome, and
- 2. the interrelations between these distinct entities both in patient management and in clinical research,
thus allowing the data to be more readily retrievable and shareable, and more able to serve in the support of algorithmic reasoning.
Goals
The goals of the workshop are:
- to utilize consistent ontological design and development principles to describe disease signs and symptoms, clinical and laboratory findings, and their interrelations.
- to delineate the roles that signs, symptoms and findings play in both clinical patient management and in clinical research.
- to develop a clear understanding and representation of the distinction between clinical and pre-clinical manifestations of signs, symptoms and findings.
- to take first steps towards harmonizing the ontological representation of disease signs and symptoms and clinical and laboratory findings with existing and emerging standards in knowledge representation from the health informatics and bioinformatics communities
- to explore incorporation of the results of this work into the CTSA Human Studies Metadata Repository framework
Agenda
Day 1: Wednesday, September 3 (Room: Irving I-III, Lobby Level)
8:30am - Registration and Continental Breakfast
9:00am - Opening remarks / Workshop goals (Richard Scheuermann)
9:15am - Session 1: Signs, symptoms and laboratory findings from a health care perspective (Scheuermann, moderator)
10:30am - Refreshment Break
10:45am - Session 2: Ontology approaches to describing the clinical phenotype slides (Smith, moderator)
- Reasoning with clinical exam and laboratory findings: The case of myocardial infarction slides (Sivaram Arabandi)
12:00pm - Buffet Lunch (Arlington Room, Lower Level), Provided by the generous support of Lead Horse Technologies, Inc.
1:00pm - Session 3: Standardization of clinical and laboratory data in the context of clinical and translational research (Jaffe, moderator)
3:00pm - Refreshment Break
3:30pm - Session 3 continued (Ruttenberg, moderator)
5:30pm - Reception (Grand Prairie Room, Lower Level), Provided by the generous support of The Cleveland Clinic Foundation SemanticDB
Day 2: Thursday, September 4 (Room: Irving I-III, Lobby Level)
8:30am - Continental Breakfast
9:00am - Session 4: Proposals for unification of standard terminologies for the representation ‘sign’, ‘symptom’, ‘finding’ and related terms (Lewis, moderator)
10:30am - Refreshment Break
10:45am - Session 5: How consistent ontological design and development principles can lead to enhanced representation of signs, symptoms, and clinical and laboratory finding (Smith, moderator)
- PATO and Phenote: From model organism phenotypes to clinical medicine slides (Suzanna Lewis)
12:00pm - Lunch Break
1:00pm - Session 6: Strategies to achieve convergence of ontologies, vocabularies and data structures in representing signs, symptoms, and clinical and laboratory findings (Scheuermann, moderator)
2:30pm - Refreshment Break
2:45pm - Session 6 (continued)
4:00pm - Close
Summary of Workshop
- Summary slides (Kei Cheung)
Participants
- Jonas Silva Almeida (MD Anderson Cancer Center / University of Texas)
- Sivaram Arabandi (Heart & Vascular Institute / Cleveland Clinic)
- John M. Armstrong (Lead Horse Technologies, Inc.)
- Robert Arp (National Center for Biomedical Ontology / University at Buffalo)
- Elmer V. Bernstam (University of Texas Health Science Center at Houston)
- Bruce Bray (Dept of Biomedical Informatics, University of Utah)
- Anita Burgun (Université de Rennes)
- Kei-Hoi Cheung (Senselab / Yale Center for Medical Informatics)
- Christopher G. Chute (National Center for Biomedical Ontology / Mayo Clinic)
- Paolo Ciccarese (Mass General Hospital / Harvard Medical School)
- Timothy W. Clark (Mass General Institute for Neurodegenerative Disease / Harvard Medical School)
- Gianluca Colombo (University of Milano-Bicocca, DISCo)
- Tommie G. Curtis (SAIC, NCICB Contractor)
- Amar K. Das (Center for Biomedical Informatics Research / Stanford University)
- Louis J. Goldberg (Ontology Research Group / University at Buffalo)
- Herb Hagler (University of Texas Southwestern Medical Center at Dallas)
- William Hogan (University of Pittsburgh Medical Center)
- Zhang-Zhi Hu (PRO / Georgetown University Medical Center)
- Charles Jaffe (Health Level 7, Inc. (HL7))
- Andrew G. James (Division of Neonatology, The Hospital for Sick Children / University of Toronto)
- David Karp (University of Texas Southwestern Medical Center at Dallas)
- Bron Kisler (CDISC)
- Megan Kong (University of Texas Southwestern Medical Center at Dallas)
- Suzanna Lewis (Lawrence Berkeley National Laboratory)
- Daniele Merico (NEUROWEB / University of Toronto & University of Milano-Bicocca, DISCo)
- Pradeep Mutalik (Yale Center for Medical Informatics)
- Chimezie Ogbuji (Cleveland Clinic Foundation)
- John Quinn (Health Level 7, Inc. (HL7))
- Alan Ruttenberg (Science Commons / Neurocommons)
- Neil Sarkar (Marine Biological Laboratory)
- Richard Scheuermann (University of Texas Southwestern Medical Center at Dallas)
- Lynn M. Schriml (Institute for Genome Sciences, University of Maryland)
- Barry Smith (National Center for Biomedical Ontology / University at Buffalo)
- Kent A. Spackman (International Health Terminology Standards Development Organization)
- Larry Streepy (Cleveland Clinic Foundation)
- Gary Walker (Quintiles)
- Ashley Xia (NIAID / NIH)
- W. Jim Zheng (Biomedical Ontology Research Group / Medical University of South Carolina)
In addition to NCBO and the University of Texas Southwestern Medical Center, the following communities are represented: CTSA, HL7, CDISC, OBO, SNOMED, and the NIH.
Suggested Background Reading
Continua in Biological Systems, Stefan Schulz and Ingvar Johansson, The Monist, 2007; 90(4), 499-522.
NEUROWEB Project: From Clinically-Based Phenotypes to Genomics Integration
OBO Foundry: Coordinated Evolution of Ontologies to Support Biomedical Data Integration
Ontology-Guided Data Preparation for Discovering Genotype-Phenotype Relationships
PhenomicDB: A New Cross-Species Genotype/Phenotype Resource
What is a Diagnosis?, Werner Ceusters
Using an Integrated Ontology and Information Model for Querying and Reasoning about Phenotypes: The Case of Autism, Samson W. Tu, Lakshika Tennakoon, Martin O'Connor, Ravi Shankar, and Amar Das.
The Factory Model of Disease, Neil Williams, The Monist, 2007; 90(4): 555-584.
Human disease classification in the postgenomic era, J. Loscalzo, I. Kohane and A.-L. Barabasi
Useful Links
Proposed Terms and Definitions
Follow-Up Meeting 2009
Signs, Symptoms and Findings: Towards an Ontology for Clinical Phenotypes