Biomedical Ontologies: Toward Scientific Debate

Summary

Objectives: Biomedical ontologies have been very successful in structuring knowl edge for many different applications, receiving widespread praise for their utility and potential. Yet, the role of computational ontologies in scientific research, as opposed to knowledge management applications, has not been extensively discussed. We aim to stimulate further discussion on the advantages and challenges presented by biomedical ontologies from a scientific perspective.

Methods: We review various aspects of biomedical ontologies going beyond their practical successes, and focus on some key scientific questions in two ways. First, we analyze and discuss current approaches to improve biomedical ontologies that are based largely on classical, Aristotelian ontological models of reality. Second, we raise various open questions about biomedical ontologies that require further research, analyzing in more detail those related to visual reasoning and spatial ontologies.

Results: We outline significant scientific issues that biomedical ontologies should consider, beyond current efforts of building practical consensus between them. For spatial ontologies, we suggest an approach for building “morphospatial” taxonomies, as an example that could stimulate research on fundamental open issues for biomedical ontologies.

Conclusions: Analysis of a large number of problems with biomedical ontologies suggests that the field is very much open to alternative interpretations of current work, and in need of scientific debate and discussion that can lead to new ideas and research directions.

Keywords

Biomedical ontologies - biomedical informatics - spatial ontologies - artificial intelligence - mathematical morphology

• References

• 1 Gómez-Pérez A, Fernandez-Lopez M, Corcho O. Ontological Engineering. Springer Verlag; 2004
• 2 Gruber TR. A Translation Approach to Portable Ontology Specifications. Knowledge Acquisition 1993; 5 (02) 199-220.
• 3 Foundational Model of Anatomy (homepage on the Internet).. Available from: http://sig.biostr. washington.edu/projects/fm. Last access: January 2011
• 4 Gene Ontology (homepage on the Internet). Available from: http://www.geneontology.org. Last access: January 2011
• 5 Lacy Lee W. OWL: Representing Information Using the Web Ontology Language. Chapter 10. Victoria, BC: Trafford Publishing; 2005
• 6 Obrst L, Cassidy P, Ray S, Smith B, Soergel D, Peter Yim P. The Upper Ontology Joint Communiqué, March 15, 2006, Version 1.02. Applied Ontology 2006; 1 (02) 203-211.
• 7 Spear AD. BFO. Manual Ontology for the Twenty-First Century: An Introduction with Recommendations. Saarbrücken, Germany; 2006
• 8 DOLCE: a Descriptive Ontology for Linguistic and Cognitive Engineering (homepage on the Internet). Available from: http://www.loa-cnr.it/DOLCE. html. Last access: January 2011
• 9 Ontology Online.. Gum: the generalized upper model (homepage on the Internet). Available from: http://ontologyonline.org/visualisation c/Directory/Gum+-+the+general-ized+upper+model/. Last access: January 2011
• 10 Overview of OpenCync (homepage on the Internet).. Available from: http://www.cyc.com opencyc/. Last access: January 2011
• 11 PSL Ontology (homepage on the Internet).. Available from: http://dream.inf.ed.ac.uk/projects/dor psl/psl.html. Last access: January 2011
• 12 Ontology Portal.. Suggested Upper Merged Ontology (SUMO)(homepage on the Internet). Available from: http://www.ontologyportal.org. Last access: January 2011
• 13 Ontologies and Theories (ontologies forum) (homepage on the Internet).. Available from: http://www-ksl.stanford.edu/email-archives/srkb. messages/133.html. Last access: January 2011
• 14 Øhrstrøm P, Andersen J, Schärfe H. What Has Happened to Ontology. Proceedings ICCS 2005 pp 425-438.
• 15 Gene Ontology Consortium.. Creating the gene ontology resource: design and implementation. Genome Res 2001 11: 1425-33.
• 16 Renear AH, Palmer CL. Strategic reading, ontologies, and the future of scientific publishing. Science 2009; 325 5942 828-832.
• 17 Rubin DL, Shah NH, Noy NF. Biomedical ontologies: a functional perspective. Brief Bioinform 2008; 9 (01) 75-90.
• 18 Liu K, Chapman WW, Savova G, Chute CG, Sioutos N, Crowley RS. Effectiveness of Lexico-syntactic Pattern Matching for Ontology Enrichment with Clinical Documents. Methods Inf Med 2010 49 (6).
• 19 Farion K, Michalowski W, Wilk S, O’Sullivan D, Rubin S, Weiss D. Clinical decision support system for point of care use – ontology-driven design and software implementation. Methods Inf Med 2009; 48 (04) 381-390.
• 20 GoPubMed (homepage on the Internet).. Available from: http://www.gopubmed.org. Last access: January 2011
• 21 Rubin DL, Lewis SE, Mungall CJ, Misra S, Wester-field M, Ashburner M, Sim I, Chute CG, Solbrig H, Storey MA, Smith B, Day-Richter J, Noy NF, Musen MA. National Center for Biomedical Ontology: advancing biomedicine through structured organization of scientific knowledge. OMICS 2006; 10 (02) 185-198.
• 22 Cimino JJ, Zhu X. The practical impact of ontologies on biomedical informatics. Yearb Med Inform 2006 pp 124-135.
• 23 Blobel B. Architectural approach to eHealth for enabling paradigm changes in health. Methods Inf Med 2010; 49 (02) 123-134.
• 24 Smith B, Brochhausen M. Putting biomedical ontologies to work. Methods Inf Med 2010; 49 (02) 135-140.
• 25 Maojo V, Crespo J, de la Calle G, Barreiro J, Garcia-Remesal M. Using web services for linking genomic data to medical information systems. Methods Inf Med 2007; 46 (04) 484-492.
• 26 Alonso-Calvo R, Maojo V, Billhardt H, Martin-Sanchez F, García-Remesal M, Pérez-Rey D. An agent-and ontology-based system for integrating public gene, protein, and disease databases. J Biomed Inform 2007; 40 (01) 17-29.
• 27 García-Remesal M, Maojo V, Billhardt H, Crespo J. Integration of Relational and Textual Biomedical Sources. Methods Inf Med 2009 48 (1).
• 28 Anguita A, Martín L, Crespo J, Tsiknakis M. An ontology based method to solve query identifier heterogeneity in post-genomic clinical trials. Stud Health Technol Inform 2008; 136: 3-8.
• 29 Pérez-Rey D, Maojo V. An Ontology-Based Method to Link Database Integration and Data Mining within a Biomedical Distributed KDD. Proceedings of AIME 2009 pp 355-359.
• 30 Maojo V, García-Remesal M, Billhardt H, AlonsoCalvo R, Pérez-Rey D, Martín-Sánchez F. Designing new methodologies for integrating biomedical information in clinical trials. Methods Inf Med 2006; 45 (02) 180-185.
• 31 García-Remesal M, Maojo V, Crespo J, Billhardt H. Logical schema acquisition from text-based sources for structured and non-structured biomedical sources integration. AMIA Annu Symp Proc 2007 pp 259-263.
• 32 García-Remesal M, Cuevas A, Pérez-Rey D, Martín L, Anguita A, de la Iglesia D, de la Calle G, Crespo J, Maojo V. PubDNA Finder: a web database linking full-text articles to sequences of nucleic acids. Bioinformatics 2010; 26 (21) 2801-2802.
• 33 García-Remesal M, Cuevas A, López-Alonso V, López-Campos G, de la Calle G, de la Iglesia D, Pérez-Rey D, Crespo J, Martín-Sánchez F, Maojo V. A method for automatically extracting infectious disease-related primers and probes from the literature. BMC Bioinformatics 2010; 11: 410.
• 34 De la Calle G, García-Remesal M, Chiesa S, de la Iglesia D, Maojo V. BIRI: a new approach for automatically discovering and indexing available public bioinformatics resources from the literature. BMC Bioinformatics 2009; 10: 320.
• 35 Pérez-Rey D, Maojo V, García-Remesal M, AlonsoCalvo R, Billhardt H, Martin-Sánchez F, Sousa A. ONTOFUSION: ontology-based integration of genomic and clinical databases. Comput Biol Med 2006; 36 7–8 712-730.
• 36 Linares Quintana A. Herramienta para el descubrimiento de efectos tóxicos de nanomateriales en aplicaciones médicas a partir de la literatura. Facultad de Informática, Universidad Politécnica de Madrid; May 2010
• 37 Brochhausen M, Spear AD, Cocos C, Weiler G, Martín L, Anguita A, Stenzhorn H, Daskalaki E, Schera F, Schwarz U, Sfakianakis S, Kiefer S, Dörr M, Graf N, Tsiknakis M. The ACGT Master Ontology and its applications – Towards an ontology-driven cancer research and management system. J Biomed Inform 2011; 44 (01) 8-25. .
• 38 Bodenreider O. Biomedical Ontologies in Action: Role in Knowledge Management, Data Integration and Decision Support. Yearb Med Inform 2008 pp 67-79.
• 39 Baclawski K, Niu T. Ontologies for Bioinformatics. The MIT Press; 2005
• 40 Ceusters W, Smith B, Kumar A, Dhaen D. Mistakes in Medical Ontologies: Where Do They Come From and How Can They Be Detected?. Stud Health Technol Inform 2004; 102: 145-163.
• 41 Köhler J, Munn K, Rüegg A, Skusa A, Smith B. Quality control for terms and definitions in ontologies and taxonomies. BMC Bioinformatics 2006; 7: 212.
• 42 Ceusters W, Smith B, Goldberg L. A terminological and ontological analysis of the NCI Thesaurus. Methods Inf Med 2005; 44 (04) 498-507.
• 43 Smith B, Ashburner M, Rosse C, Bard J, Bug W, Ceusters W, Goldberg LJ, Eilbeck K, Ireland A, Mun-gall CJ, Consortium OBI, Leontis N, Rocca-Serra P, Ruttenberg A, Sansone SA, Scheuermann RH, Shah N, Whetzel PL, Lewis S. The OBO Foundry: coordinated evolution of ontologies to support biomedical data integration. Nat Biotechnol 2007; 25 (11) 1251-1255.
• 44 Schober D, Smith B, Lewis SE, Kusnierczyk W, Lomax J, Mungall C, Taylor CF, Rocca-Serra P, Sansone SA. Survey-based naming conventions for use in OBO Foundry ontology development. BMC Bioinformatics 2009; 10: 125.
• 45 Smith B, Ceusters W, Klagges B, Köhler J, Kumar A, Lomax J, Mungall C, Neuhaus F, Rector AL, Rosse C. Relations in biomedical ontologies. Genome Biol 2005; 6 (05) R46.
• 46 Smith B. Principles of biomedical ontology design (homepage on the Internet). Available from: http://www.geneontology.org/minutes/20060331_ AdditionalMaterial/presentations/ontology-design _bsmith.ppt. Last access: January 2011
• 47 Hawthorne J. Three-Dimensionalism vs Four-Dimensionalism. In: Sider T, Hawthorne J, Zimmerman DW. (eds.). Contemporary Debates in Metaphysics Blackwell Pub;. 2008 pp 263-282.
• 48 Miller M. The Metaphysical Equivalence of Three and Four Dimensionalism. Erkenntnis 2005; 62: 91-117.
• 49 Fine K. In Defence of Three-Dimensionalism. Royal Institute of Philosophy Supplement 2008; 83: 1-16.
• 50 Reydon TA. Species in three and four dimensions. Synthese 2008; 164: 161-184.
• 51 Grenon P, Smith B. SNAP and SPAN: Towards Dynamic Spatial Ontology. Spatial Cognition & Computation: An Interdisciplinary Journal 2004; 4 (01) 69-104.
• 52 Niggemann JG, Gebert A, Schulz S. Modeling Functional Neuroanatomy for an Anatomy Information System. JAMIA 2008; 15: 671-678.
• 53 Rosse C, Mejino Jr JL. A reference ontology for biomedical informatics: the Foundational Model of Anatomy. J Biomed Inform 2003; 36 (06) 478-500.
• 54 Feynman RP. The Feynman Lectures on Computation. Hey AJG Allen RW(eds). Reading, MA: Addison-Wesley; 1996
• 55 Prigogine I, Stengers I. Order out of Chaos: Man’s new dialogue with nature. Bantam: Toronto, Canada; 1984
• 56 Wiener N. Cybernetics or Control and Communication in the Animal and the Machine. Hermann & Cie Eds Paris: The Technology Press; Cambridge, Mass., John Wiley & Sons Inc., New York; 1948
• 57 Patrick J. Metonymic and Holonymic Roles and Emergent Properties in the SNOMED CT Ontology. The Australasian Ontology Workshop (AOW 2006). Hobart, Tasmania, Australia: Conferences in Research and Practice in Information Technology, Vol. 72. Mehmet Orgun & Thomas Meyer, Eds.
• 58 Russell B. Impact of Science on Society. Routledge; 1985
• 59 Numbers R. Galileo goes to jail and Other Myths about Science and Religion. Harvard University Press: 1st ed; 2009
• 60 Bunge M. Emergence and convergence. University of Toronto Press: Toronto, Canada; 2003
• 61 Mahner M, Bunge M. Foundations of Biophilosophy. Berlín, Germany: Springer; 1997
• 62 Eilbeck K, Lewis SE, Mungall CJ, Yandell M, Stein L, Durbin R, Ashburner M. The Sequence Ontology: a tool for the unification of genome annotations. Genome Biol 2005; 6 (05) R44.
• 63 Monod J. Chance and Necessity: An Essay on the Natural Philosophy of Modern Biology. New York: Alfred A Knopf; 1971
• 64 Lorenz K. Behind the mirror. New York, NY: Mariner Books; 1978
• 65 López Rodriguez D. Extensión de la capa de mediación semántica en la plataforma de ensayos clínicos ACGT. Facultad de Informática, Universidad Politécnica de Madrid; September 2010
• 66 Sandholm T. The Philosophy of the Grid: Ontology Theory – From Aristotle to Self-Managed IT Resources: Royal Institute of Technology: Technical Report TRITA-NA-0532. 2005
• 67 Goguen, Ontotheology, Ontology, and Society (homepage on the Internet). Available from: cseweb.ucsd.edu/~goguen/pps/onto5.pdf. Last access: January 2011
• 68 Mayr E. What makes biology unique?. Cambridge, UK: Cambridge University Press; 2004
• 69 Bohr N. Atomic Physics and Human Knowledge. New York, USA: Science Edition; 1961
• 70 Minsky M. The Society of Mind. New York, NY: Simon and Schuster; 1988
• 71 Simon HA, Kaplan CA. C. A. in Foundations of Cognitive Science. M. Posner (ed). Cambridge, MA: MIT Press; 1990
• 72 Lehn JM. Toward Self-Organization and Complex Matter. Science 2002; 29 295 5564 2400-2403.
• 73 Hartmann N. New ways of ontology. Westport, CT: Greenwood Press; 1952
• 74 Schulz S, Boeker M, Stenzhorn H. How granularity issues concern biomedical ontology integration. Stud Health Technol Inform 2008; 136: 863-868.
• 75 KEGG: Kyoto Encyclopedia of Genes and Genomes (homepage on the Internet). Available from: http://www.genome.jp/kegg. Last access: January 2011
• 76 Rector A, Rogers J, Bittner T. Granularity, scale and collectivity: When size does and does not matter. Journal of Biomedical Informatics 2006; 39: 333-349.
• 77 Pal D. On gene ontology and function annotation. Bioinformation 2006; 1 (03) 97-98.
• 78 Noble D. The Music of Life. Oxford University Press; 2006
• 79 Noble D. Claude Bernard, the first systems biologist, and the future of physiology. Exp Physiol 2008; 93 (01) 16-26.
• 80 Miller K. The Physiome. A mission imperative. Biomedical Computation Review 2010 pp 8-15.
• 81 Smith B. Ontology. Nature precedings (homepage on the Internet). Available from: precedings.nature.com/documents/2027/version/2. Last access: January 2011
• 82 Rosse C, Mejino JLV. The Foundational Model of Anatomy Ontology. Anatomy Ontologies for Bioinformatics: Principles and Practice. Burger A, Davidson, Baldock R. (eds) Springer; London: 2007. 6 59-117.
• 83 Spear AD. BFO. Manual Ontology for the Twenty-First Century: An Introduction with Recommendations. Saarbrücken, Germany; 2006
• 84 Akkermans H, Gordijn J. Ontology Engineering, Scientific Method and the Research Agenda. In: Staab S, Svatek VB. (eds). EKAW2006, LNAI 4248. 112-125. 2006. Berlin Heidelberg: Springer-Verlag; 2006
• 85 Hogan WR. Towards an ontological theory of substance intolerance and hypersensitivity. J Biomed Inform 2011; 44 (01) 26-34. .
• 86 Johansson I, Smith B, Tsikolia N. et al. Functional Anatomy. A Taxonomic Proposal. Acta Biotheoretica 2005; 53 (03) 153-166.
• 87 Gennari J, Neal M, Carlson BE, Cook D. Integration of multi-scale biosimulation models via lightweight semantics. Pacific Symposium on Biocomputing 2008; 13: 414-425.
• 88 Grenon P, Smith B. A Formal Theory of Substances, Qualities and Universals. In: Varzi A, Vieu L. (eds). Proceedings of FOIS 2004 (International Conference on Formal Ontology and Information Systems), Turin: 2004
• 89 Metzinger T, Gallese V. The emergence of a shared action ontology: building blocks for a theory. Conscious Cogn 2003; 12 (04) 549-571.
• 90 Kuhn T. The Structure of Scientific Revolutions. 2nd ed. Chicago, USA: University of Chicago Press; 1970
• 91 Maojo V, Kulikowski CA. Reflections on biomedical informatics: from cybernetics to genomic medicine and nanomedicine. Proceedings of the Medical Informatics Europe 2006; 124: 19-24.
• 92 Deutsch D. The Fabric of Reality: The Science of Parallel Universes – And Its Implications. London, UK: Penguin Books; 1997
• 93 Hugget N. Everywhere and Everywhen. Adventures in Physics and Philosophy. Oxford University Press; 2010
• 94 Müller-Wille S. Hybrids, pure cultures, and pure lines: from nineteenth-century biology to twentieth-century genetics. Stud Hist Philos Biol Biomed Sci 2007; 38 (04) 796-806.
• 95 Lederberg J. How Dendral Was Conceived and Born. ACM Symposium on the History of Medical Informatics, Rockefeller University. New York: National Library of Medicine; 1987
• 96 Lindsay RK, Buchanan B, Feigenbaum EA, Lederberg J. DENDRAL: A Case Study of the First Expert System for Scientific Hypothesis Formation. Artificial Intelligence 1993; 61 (02) 209-261.
• 97 Kulikowski C, Weiss S. Computer-based Models of Glaucoma Report no 3. Department of Computer Science, Computers in Biomedicine. New Brunswick, NJ: Rutgers University; 1971
• 98 Shortliffe EH. Computer-Based Medical Consultations: MYCIN. New York, USA: Elsevier; 1976
• 99 Miller RA, Masarie Jr FE. The demise of the “Greek Oracle” model for medical diagnostic systems. Methods Inf Med 1990; 29 (01) 1-2.
• 100 Lenat DB. AM. Ph. D. Thesis, AIM-286, STAN-CS-76–570, and Heuristic Programming Project Report HPP-76–8. Stanford University, AI Lab., Stanford, CA; 1976
• 101 Woods WA. What’s in a Link: Foundations for Semantic Networks. Bobrow DG Collins AM (eds). Representation and Understanding. Academic Press; 1975
• 102 Allan M, Collins A, Quillian MR. Retrieval time from semantic memory. Journal of verbal learning and verbal behavior 1969; 8 (02) 240-248.
• 103 Sowa JF, Borgida A. Principles of Semantic Networks: Explorations in the Representation of Knowledge. 1991
• 104 Cook DL, Mejino JL, Neal ML, Gennari JH. Bridging biological ontologies and biosimulation: the ontology of physics for biology. AMIA Annu Symp Proc 2008; 6: 136-140.
• 105 Kuipers B. Qualitative simulation. Artificial Intelligence 1986; 29 (03) 289-338.
• 106 Forbus KD. Interpreting Measurements of Physical Systems. AAAI; 1986. pp 113-117.
• 107 Long WJ. Reasoning About State from Causation and Time in a Medical Domain. Proceedings of National Joint Conference on Artificial Intelligence (AAAI-83); 1983
• 108 Widman LE. Expert system reasoning about dynamic systems by semi-quantitative simulation. Comput Methods Programs Biomed 1989; 29 (02) 95-113.
• 109 Langley P, Simon HA, Bradshaw GL, Zytkow JM. Scientific discovery: Computational explorations of the creative processes. MIT Press: London; 1987
• 110 Loveland DW. Automated Theorem Proving: A Logical Basis. Fundamental Studies in Computer Science, Volume 6. North-Holland Publishing; 1978
• 111 Stearn WT. The Background of Linnaeus’s Contributions to the Nomenclature and Methods of Systematic Biology. Systematic Zoology 1959; 8: 4-22.
• 112 Mungall CJ, Batchelor C, Eilbeck K. Evolution of the Sequence Ontology terms and relationships. J Biomed Inform 2011; 44 (01) 87-93..
• 113 Rosse C, Kumar A, Mejino Jr JL, Cook DL, Detwiler LT, Smith B. A strategy for improving and integrating biomedical ontologies. AMIA Annu Symp Proc 2005; pp 639-643.
• 114 Johansson I. Bioinformatics and biological reality. J Biomed Inform 2006; 39 (03) 274-287.
• 115 Smith B, Köhler J, Kumar A. On the Application of Formal Principles to Life Science Data: A Case Study in the Gene Ontology. Rahm E (ed.). Database Integration in the Life Sciences (DILS 2004). Berlin: Springer; 2004
• 116 Diehl AD, Augustine AD, Blake JA, Cowell LG, Gold ES, Gondré-Lewis TA, Masci AM, Meehan TF, Morel PA, Nijnik A, Peters B, Pulendran B, Scheuermann RH, Yao QA, Zand MS, Mungall CJ. Hematopoietic cell types: Prototype for a revised cell ontology. J Biomed Inform 2011; 44 (01) 75-79. .
• 117 Gupta A, Larson SD, Condit C, Gupta S, Fong L, Chen L, Martone ME. Toward An Ontological Database for Subcellular Neuroanatomy. 1st Int Workshop on Conceptual Modeling for Life Sciences Applications (CMLSA). Auckland, New Zealand: 2007
• 118 Shafer G. A Mathematical Theory of Evidence. Princeton University Press; 1976
• 119 Zadeh LA. Fuzzy sets. Information and Control 1965; 8 (03) 338-353.
• 120 Costa P, Laskey KB, Alghamdi G. Bayesian Ontologies in AI Systems. Proceedings of the Fourth Bayesian Modelling Applications Workshop, Twenty-Second Conference on Uncertainty in Artificial Intelligence (UAI 2006). July, 13 2006, Cambridge, MA, USA.:
• 121 Stoilos G, Simou N, Stamou G, Kollias S. Uncertainty and the Semantic Web. IEEE Intelligent Systems 2006; 21: 84-87.
• 122 PATO – Phenotypic Quality Ontology, from Wikipedia [homepage on the Internet]. Available from: http://obofoundry.org/wiki/index.php/PATO_Main_Page. Last access: January 2011
• 123 Zhongli D. et al. A Bayesian Approach to Uncertainty Modeling in OWL Ontology. Proceedings of the International Conference on Advances in Intelligent Systems – Theory and Applications. November 2004
• 124 Ceusters W, Cimino J, Rector A. Medical Language and Terminologies. In: Sosa-Iudicissa M, Oliveri N, Gamboa CA, Roberts J. (eds). Internet, Telematics and Health. Amsterdam: IOS Press; 1997. pp 197-203.
• 125 Planck M. Scientific Autobiography and other papers. Philosophical Library; 1968
• 126 Smith B. The Evaluation of Ontologies: Editorial Review vs. Democratic Ranking. Proceedings of InterOntology 2008: 127-138. Tokyo, Japan: 26-27 February 2008
• 127 Spatial Ontology.. The Open Biological and Biomedical Ontologies (homepage on the Internet). Available from: http://www.obofoundry.org/cgi-bin/detail.cgi?id=spatial. Last access: January 2011
• 128 Spatial Ontology Community of Practice Wiki (homepage on the Internet). Available from: http://ontolog.cim3.net/cgi-bin/wiki.pl?SOCoP. Last access: January 2011
• 129 Schulz S, Boeker M, Stenzhorn H, Niggemann J. Granularity issues in the alignment of upper ontologies. Methods Inf Med 2009; 48 (02) 184-189.
• 130 Borgo S, Guarino N, Masolo C. An Ontological Theory of Physical Objects. Proceedings of Qualitative Reasoning. 11th International Workshop; 1997
• 131 Bittner T, Goldberg LJ. The qualitative and time-dependent character of spatial relations in biomedical ontologies. Bioinformatics 2007; 23 (13) 1674-1682.
• 132 Gonzalez RC, Woods RE. Digital image processing. Prentice Hall: 2nd ed; 2002
• 133 Jain AK. Fundamentals of Digital Image Processing. Prentice Hall; 1988
• 134 Soille P. Morphological Image Analysis: Principles and Applications. Heidelberg: Springer, 2nd ed; 2003
• 135 Klette R, Rosenfeld A. Digital Geometry: Geometric Methods for Digital Picture Analysis. Morgan Kaufmann; 2004
• 136 Duda RO, Hart PE, Stork DG. Pattern Classification. 2nd. ed; 2000
• 137 Liu Y, Zhang J, Tjondronegoro D, Geve S. A Shape Ontology Framework for Bird Classification. Proceedings of the 9th Biennial Conference of the Australian Pattern Recognition Society on Digital Image Computing Techniques and Applications 2007 pp 478-484.
• 138 Lorenzatti A, Abel M, Nunes B, Scherer C. Ontology for Imagistic Domains: Combining Textual and Pictorial Primitives. Lecture Notes in Computer Science 2009; 5833: 169-178.
• 139 Cohn AG, Bennett B, Gooday JM, Gotts N. RCC: A Calculus for region based qualitative spatial reasoning. GeoInformatica 1997; 1: 275-316.
• 140 Davis E. The expressivity of quantifying over regions. J Logic and Computation 2006; 16: 891-916.
• 141 Douglas M, Kolodny-Hirsch, Van Beek NAM. A Morphological Variant of Autographa Californica Nuclear Polyhedrosis Virus with Increased Virulence Following Serial Passage in Plutella xylostella. Journal of Invertebrate Pathology 1997; 69 (03) 205-211.
• 142 Munn K, Smith B. Applied Ontology. Ontos Verlag; 2008
• 143 Simons P. Ontology meets ontologies: philosophers as healers. Metascience 2009; 18: 469-473.
• 144 Leaving BFO Discuss, P. Lord (homepage on the Internet). Available from: http://www.russet.org.uk/blog/2010/03/23/. Last access: January 2011
• 145 Feynman R. The Feynam Lectures on Physics, Vol. 2. Addison-Wesley; 1977
• 146 Ackerman JM, Nocera CC, Bargh JA. Incidental haptic sensations influence social judgments and decisions. Science 2010; 328 5986 1712-1715.
• 147 Hadamard J. The Psychology of Invention in the Mathematical Field. Dover; 1954
• 148 Posner M. Foundations of Cognitive Science. Cambridge, MA: The MIT Press; 1990
• 149 Khatri P, Draghici S. Ontological analysis of gene expression data: current tools, limitations, and open problems. Bioinformatics 2005; 21 (18) 3587-3595.
• 150 McCray AT. Conceptualizing the world: lessons from history. J Biomed Inform 2006; 39 (03) 267-273.
• 151 Ingenerf J, Linder R. Assessing applicability of ontological principles to different types of biomedical vocabularies. Methods Inf Med 2009; 48 (05) 459-67.
• 152 Zweigenbaum P, Bachimont B, Bouaud J, Charlet J, Boisvieux JF. Issues in the structuring and acquisition of an ontology for medical language understanding. Methods Inf Med 1995; 34 1–2 15-24.
• 153 Russell S, Norvig P. Artificial Intelligence. A modern approach. Third edition: Prentice Hall; 2010