Effective Ontology Construction: Key Principles & Applications

1. What is Ontology? • Dictionary:A branch of metaphysics concerned with the nature and relations of being. • Barry Smith:The science of what is, of the kinds and structures of objects, properties, events, processes and relations in every area of reality. 1606 1700s

2. So what does that mean? From a practical view, ontology is the representation of something we know about. “Ontologies" consist of a representation of things, that are detectable or directly observable, and the relationships between those things. is part of

3. The GO is Actually Three Ontologies Molecular Function GO term: Malate dehydrogenase. GO id: GO:0030060 (S)-malate + NAD(+) = oxaloacetate + NADH. Cellular Component GO term: mitochondrion GO id: GO:0005739 Definition: A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. Biological Process GO term: tricarboxylic acid cycle Synonym: Krebs cycle Synonym: citric acid cycle GO id: GO:0006099

4. Seven Healthy Habits of Highly Effective Ontology Construction • Univocity • Positivity • Objectivity • Single Inheritance • Create Good Definitions • Distinguish Between Types & Instances • Basis in Reality

5. GO Definitions: Each GO term has 2 Definitions A definition written by a biologist: necessary & sufficient conditions written definition (not computable) Graph structure: necessary conditions formal (computable)

6. Appropriate Relationships to Parents • GO currently has 2 relationship types • Is_a • An is_a child of a parent means that the child is a complete type of its parent, but can be discriminated in some way from other children of the parent. • Part_of • A part_of child of a parent means that the child is always a constituent of the parent that in combination with other constituents of the parent make up the parent.

7. Placement in the Graph: Selecting Parents • To make the most precise definitions, new terms should be placed as children of the parent that is closest in meaning to the term. • To make the most complete definitions, terms should have all of the parents that are appropriate. • In an ontology as complicated as the GO this is not as easy as it seems.

8. nucleus Part_of relationship True Path Violations Create Incorrect Definitions ..”the pathway from a child term all the way up to its top-level parent(s) must always be true". chromosome

9. Is_a relationship Mitochondrial chromosome True Path Violations ..”the pathway from a child term all the way up to its top-level parent(s) must always be true". chromosome

10. nucleus Part_of relationship Is_a relationship Mitochondrial chromosome True Path Violations ..”the pathway from a child term all the way up to its top-level parent(s) must always be true". A mitochondrial chromosome is not part of a nucleus! chromosome

11. nucleus chromosome mitochondrion Part_of relationship Part_of relationship Is_a relationships Nuclear chromosome Mitochondrial chromosome True Path Violations ..”the pathway from a child term all the way up to its top-level parent(s) must always be true".

12. The Development Node

13. Organism/organ/tissue level [i]x development ---[p] x morphogenesis ------[p] x formation ---------[p] y cell differentiation ------[p] x structural organization ---[p] x maturation

14. Cell level [i] y cell differentiation ---[p] y cell fate commitment ------[p] y cell fate specification ------[p] y cell fate determination ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation

15. Regulation terms [i] y cell differentiation ---[p] regulation of y cell differentiation ------[i] positive regulation of y cell differentiation ------[i] negative regulation of y cell differentiation

16. x development The process whose specific outcome is the progression of the x over time, from its formation to the mature structure. [i]x development ---[p] x morphogenesis ------[p] x formation ------[p] x structural organization ---[p] x maturation zygote http://www.dof.virginia.gov/images/ http://hypertextbook.com/chaos/33.shtml

17. x morphogenesis The process by which the anatomical structures of x are generated and organized. Morphogenesis pertains to the creation of form. [i]x development ---[p] x morphogenesis ------[p] x formation ------[p] x structural organization ---[p] x maturation http://www.campdevanol.com/blogger/archives/2005_05_01_campdevanol_archive.html

18. x formation The process that gives rise to x. This process pertains to the initial formation of a structure from unspecified parts. [i]x development ---[p] x morphogenesis ------[p] x formation ------[p] x structural organization ---[p] x maturation Limb bud http://www.sciencemuseum.org.uk/exhibitions/lifecycle/images/1-2-1-2-1-1-0-0-0-0-0.jpg

19. x structural organization The process that contributes to creating the structural organization of x. This process pertains to the physical shaping of a rudimentary structure. [i]x development ---[p] x morphogenesis ------[p] x formation ------[p] x structural organization ---[p] x maturation http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_Ch05/fig5_20.jpg

20. x maturation A developmental process, independent of morphogenetic (shape) change, that is required for x to attain its fully functional state. [description of x] [i]x development ---[p] x morphogenesis ------[p] x formation ------[p] x structural organization ---[p] x maturation http://www.dof.virginia.gov/images/

21. y cell differentiation The process whereby a relatively unspecialized cell acquires specialized features of a y cell. [i] y cell differentiation ---[p] y cell fate commitment ------[p] y cell fate specification ------[p] y cell fate determination ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=cmed6.figgrp.41173

22. y cell fate commitment The process whereby the developmental fate of a cell becomes restricted such that it will develop into a y cell. [i] y cell differentiation ---[p] y cell fate commitment ------[p] y cell fate specification ------[p] y cell fate determination ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation

23. y cell fate specification The process whereby a cell becomes capable of differentiating autonomously into a y cell in an environment that is neutral with respect to the developmental pathway. Upon specification, the cell fate can be reversed. [i] y cell differentiation ---[p] y cell fate commitment ------[p] y cell fate specification ------[p] y cell fate determination ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation

24. y cell fate determination The process whereby a cell becomes capable of differentiating autonomously into a y cell regardless of its environment; upon determination, the cell fate cannot be reversed. [i] y cell differentiation ---[p] y cell fate commitment ------[p] y cell fate specification ------[p] y cell fate determination ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation

25. y cell development The process aimed at the progression of a y cell over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell. [i] y cell differentiation ---[p] y cell fate commitment ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation

26. y cell morphogenesis during differentiation The process by which the structures of a y cell are generated and organized. This process occurs while the initially relatively unspecialized cell is acquiring the specialized features of a y cell. [i] y cell differentiation ---[p] y cell fate commitment ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation http://www.nature.com/ncb/journal/v6/n8/images/ncb0804-707-I1.jpg

27. y cell maturation A developmental process, independent of morphogenetic (shape) change, that is required for a y cell to attain its fully functional state. [description of y] [i] y cell differentiation ---[p] y cell fate commitment ------[p] y cell fate specification ------[p] y cell fate determination ---[p] y cell development ------[p] y cellular morphogenesis during differentiation ------[p] y cell maturation

28. is_a completeness Logically, everything that exists is a sub-type of something else. (There’s a prize if you can think of an exception.)