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Processing Function Terms

Processing Function Terms. Amelia Ireland. Function Problems. Function-process crossover Function and process are not orthogonal Functions appear in process and vice versa The ‘One Step Rule’ ‘Steps’ vary between terms ‘Clean’ and ‘dirty’ functions

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Processing Function Terms

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  1. Processing Function Terms Amelia Ireland

  2. Function Problems • Function-process crossover • Function and process are not orthogonal • Functions appear in process and vice versa • The ‘One Step Rule’ • ‘Steps’ vary between terms • ‘Clean’ and ‘dirty’ functions • Many functions don’t fit the def ‘elemental activities describing the actions of a gene product at the molecular level’ • GO function is not what people mean when they talk about the ‘function of a protein’

  3. The Proposal • Move function terms representing steps in a process into the process ontology

  4. Function Problems • Function-process crossover • Function and process are not orthogonal • Functions appear in process and vice versa • The ‘One Step Rule’ • ‘Steps’ vary between terms • ‘Clean’ and ‘dirty’ functions • Many functions don’t fit the def ‘elemental activities describing the actions of a gene product at the molecular level’ • GO function is not what people mean when they talk about the ‘function of a protein’

  5. The Process-Function Crossover • Functions in process • Detection • The series of events in which a stimulus type stimulus is received by a cell and converted into a molecular signal. • i.e. binding during a signaling pathway • Metabolism • The chemical reactions involving xxx • binding is a chemical reaction • chemical reactions ‘involving’ xxx limits metabolism to reactions in which X is the product or those where X is the reactant, i.e. one step reactions • Many terms under ‘protein modification’

  6. The Function-Process Crossover • Processes in function • ent-kaurene oxidase activity,1.14.13.78 • Catalysis of three successive oxidations of the 4-methyl group of ent-kaurene resulting in kaurenoic acid. • ent-kaur-16-ene + NADPH + O2 = ent-kaur-16-en-19-ol + NADP+ + H2O • ent-kaur-16-en-19-ol + NADPH + O2 = ent-kaur-16-en-19-al + NADP+ + 2 H2O • ent-kaur-16-en-19-al + NADPH + O2 = ent-kaur-16-en-19-oate + NADP+ + H2O

  7. The Process-Function Crossover • Identical processes and functions • histone H3-K4 methylation • The modification of histone H3 by addition of a methyl group to lysine at position 4 of the histone. • histone lysine N-methyltransferase activity (H3-K4 specific) • Catalysis of the addition of a methyl group onto lysine at position 4 of the histone H3 protein.

  8. Function Problems • Function-process crossover • Function and process are not orthogonal • Functions appear in process and vice versa • The ‘One Step Rule’ • ‘Steps’ vary between terms • ‘Clean’ and ‘dirty’ functions • Many functions don’t fit the def ‘elemental activities describing the actions of a gene product at the molecular level’ • GO function is not what people mean when they talk about the ‘function of a protein’

  9. The ‘One Step’ Rule • Currently use the ‘one step rule’ to decide between process and function • One step --> function • More than one step --> process • But what level should the ‘steps’ be at?

  10. The ‘One Step’ Rule One step… or many? fructose-bisphosphate aldolase activity http://www.bu.edu/aldolase/lab/aldolase/intro/mechanism.html

  11. The ‘One Step’ Rule One step… or many? glycerol-3-phosphate transporter activity (1) an inorganic phosphate (Pi) from the periplasm binds to Co; (2) the Co pore increases in diameter; (3) a G3P binds to the Co and brings the enlarged Co pore to normal size; (4) the Co pore continues to decrease in diameter until it closes completely, which forces the G3P to the cytoplasmic end where it attaches to the Ci end; (5) the Ci pore enlarges to a certain point; (6) the Ci pore decreases in size and forces a Pi out of the cytoplasm. http://student.biology.arizona.edu/honors2004/group02/home02.html

  12. Function Problems • Function-process crossover • Function and process are not orthogonal • Functions appear in process and vice versa • The ‘One Step Rule’ • ‘Steps’ vary between terms • ‘Clean’ and ‘dirty’ functions • Many functions don’t fit the def ‘elemental activities describing the actions of a gene product at the molecular level’ • GO function is not what people mean when they talk about the ‘function of a protein’

  13. Clean and Dirty Functions • molecular function • Elemental activities, such as catalysis or binding, describing the actions of a gene product at the molecular level. A given gene product may exhibit one or more molecular functions. • Two kinds of function term • “Clean”: steps in a process • “Dirty”: combination of two or more process, function or other attributes

  14. ‘Clean’ Functions ornithine-oxo-acid transaminase activity GO:0004587 arginase activity GO:0004053 • arginine catabolism to glutamate • arginase activity • ornithine-oxo-acid transaminase activity • 1-pyrroline-5-carboxylate dehydrogenase activity 1-pyrroline-5-carboxylate dehydrogenase activity GO:0003842 arginine catabolism to glutamate ; GO:0019544 MetaCyc:ARGASEDEG-PWY arginine degradation I (arginase pathway)

  15. ‘Clean’ Functions • Notch signaling pathway • Delta binding • Notch binding • Notch receptor processing Notch signaling pathway ; GO:0007219 Notch binding ; GO:0005112 Delta binding ; GO:new Notch receptor processing GO:0007220 (process term)

  16. ‘Dirty’ Functions • Not steps in a process • Represent a combination of two or more attributes from function, component, process or other domain • May be occurrents (events) or continuants (entities)

  17. ‘Dirty’ Functions • transcription factor activity • Any activity required to initiate or regulate transcription; includes the actions of both gene regulatory proteins as well as the general transcription factors. • i.e. a role in regulation of transcription or transcription initiation • receptor activity • Combining with an extracellular or intracellular messenger to initiate a change in cell activity. • i.e. binding in a signaling pathway

  18. ‘Dirty’ Functions • ‘structural molecule activity’, ‘enzyme regulator activity’, ‘hormone activity’, ‘protein tag’ have similar problems • Dirty functions represent a role or a class and cannot be linked to process terms using existing GO relationships

  19. Function Problems • Function-process crossover • Function and process are not orthogonal • Functions appear in process and vice versa • The ‘One Step Rule’ • ‘Steps’ vary between terms • ‘Clean’ and ‘dirty’ functions • Many functions don’t fit the def ‘elemental activities describing the actions of a gene product at the molecular level’ • GO function is not what people mean when they talk about the ‘function of a protein’

  20. Proposed Solution • Move terms representing events into the process ontology

  21. Catalytic activities • Terms would be rehomed under ‘metabolism’ metabolism • hydrolase activity • isomerase activity • ligase activity • lyase activity • oxidoreductase activity • transferase activity

  22. Catalytic activities • Individual reactions could be organised according to substances involved arginine metabolism • arginine biosynthesis • argininosuccinate lyase activity • D-nopaline dehydrogenase activity • arginine catabolism • arginase activity • arginine 2-monooxygenase activity

  23. Catalytic activities • Reactions could be put into pathways arginine catabolism • arginase catabolism to glutamate • 1-pyrroline-5-carboxylate dehydrogenase activity • arginase activity • ornithine-oxo-acid transaminase activity • Data from MetaCyc, FIGS, KEGG?

  24. Catalytic activities • Reactions in more than one pathway arginase activity • arginase activity during arginine catabolism to glutamate • arginase activity during arginine catabolism to pyruvate

  25. Binding • Binding terms could be rehomed under ‘metabolism’ • metabolism • amine metabolism • amine binding • binding • amine binding

  26. Binding • Binding terms can now be linked with signaling pathways and other processes • Notch signaling pathway • Notch binding during Notch signaling pathway • Delta binding during Notch signaling pathway • Notch receptor processing

  27. …and the rest • Transporter activity • xxx transporter activity --> xxx transport • xxx permease activity --> permease-mediated xxx transport • Receptor activity • ligand binding during signaling pathway • Regulator activity • regulation

  28. …and the rest • Reinstate some obsoletes • Cell adhesion molecule --> cell adhesion receptor binding during cell-cell adhesion

  29. Synonyms • All moved terms will be given many synonyms in both process and function ‘style’ • e.g. glucose dehydrogenase, glucose dehydrogenation • glucose carrier, carrier-mediated glucose transport

  30. Brave New Function World • Redefine function • Various dictionary definitions of function: • the special, normal, or proper physiologic activity of a gene product • the actions and activities assigned to or required or expected of a gene product • what a gene product is used for • the purpose, role, or function a gene product serves • The purpose or role a gene product serves in the normal physiologic activity of an organism. A gene product may have one or more functions.

  31. Proposed Solution • Keep ‘dirty’ terms representing combinations of function, process or other information in function • New function def would allow us to add useful terms currently not allowed • toxin • ligand • other suggestions?

  32. Brave New Function World • energy transducer • enzyme • motor • nutrient reservoir • signal • chemoattractant • chemorepellant • hormone • ligand • morphogen • protein tag • structural molecule • receptor • regulator • chaperone regulator • enzyme regulator • transcription regulator • translation regulator • transporter • toxin

  33. Processed Functions Notch signaling pathway ; GO:0007219 Process: Notch binding ; GO:0005112 function: ligand process: Delta binding ; GO:new function: receptor

  34. Processed Functions ornithine-oxo-acid transaminase activity enzyme arginase activity enzyme 1-pyrroline-5-carboxylate dehydrogenase activity enzyme arginine catabolism to glutamate ; GO:0019544 MetaCyc:ARGASEDEG-PWY arginine degradation I (arginase pathway)

  35. Pros and Cons • reactions involving a certain substrate can all be homed underneath ‘xxx metabolism’ • reactions can be linked to pathways • greater precision in annotation • ontologies more consistent and ‘pure’ • less redundancy between process and function • GO function closer to colloquial interpretation

  36. Pros and Cons • some adjustment needed by those accustomed to seeing binding and enzymatic reactions in function • may take some time to implement • no obsoletions L

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