Transcript Processing Function Terms

Processing Function Terms
Amelia Ireland
The Proposal
• Move function terms representing steps in
a process into the process ontology
Function Problems
• Function and process are not orthogonal
 Processes are made up of functions
• Many functions don’t fit the def ‘elemental
activities describing the actions of a gene
product at the molecular level’
 ‘transcription factor’ is not an activity
• ‘one step’ rule for functions is too arbitrary
• GO function is not what people mean when they
talk about the ‘function of a protein’
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
‘Clean’ Functions
arginine catabolism to glutamate ; GO:0019544
arginase activity
GO:0004053
ornithine-oxo-acid
transaminase activity
GO:0004587
1-pyrroline-5-carboxylate
dehydrogenase activity
GO:0003842
MetaCyc:ARGASEDEG-PWY arginine degradation I (arginase pathway)
‘Clean’ Functions
smoothened signaling pathway ; GO:0007224
patched binding
hedgehog binding
protein binding
smoothened binding
from KEGG Hedgehog signaling pathway, ko04340
‘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. 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 + regulation of cellular process
‘Dirty’ Functions
• Dirty functions aren’t steps in a pathway
 ‘receptor activity’ is more than just binding; it
is binding in the context of a signaling
pathway
 ‘transcription factor activity’ describes a role
within the process of transcription, not a step
 ‘structural molecule activity’, ‘enzyme
regulator activity’, ‘hormone activity’ have
similar problems
The Process-Function Crossover
• 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?
The Process-Function Crossover
One step… or many?
fructose-bisphosphate aldolase activity
http://www.bu.edu/aldolase/lab/aldolase/intro/mechanism.html
The Function-Process Crossover
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
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
 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
 Many terms under ‘protein modification’
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.
The Function-Process Crossover
•
Processes in function
 ent-kaurene oxidase activity, 1.14.13.78

Catalysis of three successive oxidations of the 4methyl group of ent-kaurene resulting in
kaurenoic acid.
1. ent-kaur-16-ene + NADPH + O2 = ent-kaur-16-en19-ol + NADP+ + H2O
2. ent-kaur-16-en-19-ol + NADPH + O2 = ent-kaur16-en-19-al + NADP+ + 2 H2O
3. ent-kaur-16-en-19-al + NADPH + O2 = ent-kaur16-en-19-oate + NADP+ + H2O
Solution
• 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.
Solution
• Move terms representing steps in a
process into the process ontology
 enzyme reactions
 transport reactions
 binding
• Link these to processes and pathways
 metacyc2go project currently under way
 Data from Ross Overbeek
 KEGG? Other sources?
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?
Processed Function Terms
 maltose metabolism ; GO:0000023
maltose binding ; GO:0000new
maltose biosynthesis ; GO:0000024
maltose synthase reaction ; GO:0050420
maltose catabolism ; GO:0000025
maltose O-acetyltransferase reaction ;
GO:0008925
maltose phosphorylase reaction ; GO:0050082
maltose alpha-D-glucosyltransferase reaction ;
GO:0047471
maltose epimerase reaction ; GO:0050558
Processed Functions
 arginine catabolism
arginine catabolism to glutamate ; GO:0019544
1-pyrroline-5-carboxylate dehydrogenase reaction
; GO:0003842
arginase reaction ; GO:0004053
ornithine-oxo-acid transaminase reaction ;
GO:0004587
New Look Function
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antioxidant
energy transducer
enzyme
 no children
molecular function unknown
motor
nutrient reservoir
signal
 chemoattractant
 chemorepellant
 hormone
 ligand
 morphogen
 protein tag
structural molecule
receptor
 children are classes of receptor
regulator
 chaperone regulator
 enzyme regulator
 transcription regulator
 translation regulator
transporter
 children are classes of transporter
toxin
triplet codon-amino acid adaptor
Processed Functions
arginine catabolism to glutamate ; GO:0019544
enzyme
enzyme
enzyme
MetaCyc:ARGASEDEG-PWY arginine degradation I (arginase pathway)
Processed Functions
smoothened signaling pathway ; GO:0007224
ligand
receptor
KEGG Hedgehog signaling pathway, ko04340
Pros and Cons
+ reactions involving a certain substrate can all be
homed underneath ‘xxx metabolism’
+ reactions can be linked to pathways
+ ontologies more consistent and ‘pure’
+ less redundancy between process and function
- some adjustment needed by those accustomed
to seeing binding and enzymatic reactions in
function