NTR? - term for "negative regulation of glucose metabolic process"

[krchristie]

It seems odd that we have the general and positive terms, but not the negative term for regulation of glucose metabolic process. We already have more specific types of negative regulation of glucose metabolic processes, so if we create the neg reg term, it will have subtypes immediately.

@pgaudet @ukemi - Any objections to creating the neg reg term?

[pgaudet]

Hi @krchristie I suppose for consistency we should have it; however, I assumed this is related to the ticket you opened in the annotation tracker, #3562, concerning Cho KW, Zhou Y, Sheng L, Rui L. Lipocalin-13 regulates glucose metabolism by both insulin-dependent and insulin-independent mechanisms. Mol Cell Biol. 2011 Feb;31(3):450-7. PMID:21135134

Looking at the abstract I think the papers talks about glucose homeostasis rather than glucose metabolism, at least according to GO's definitions.

I also think 'metabolic process' is not really useful as an annotation, if we dont know whether a protein is involved in synthesizing or degrading a compound then we should probably not annotate it. And regulation is even more indirect.

To discuss on a call ?

Thanks, Pascale

[krchristie]

Hi @krchristie I suppose for consistency we should have it

I think it would be helpful in searching.

I assumed this is related to the ticket you opened in the annotation tracker, #3562, concerning Cho KW, Zhou Y, Sheng L, Rui L. Lipocalin-13 regulates glucose metabolism by both insulin-dependent and insulin-independent mechanisms. Mol Cell Biol. 2011 Feb;31(3):450-7. PMID:21135134

You are correct.

Looking at the abstract I think the papers talks about glucose homeostasis rather than glucose metabolism, at least according to GO's definitions.

Perhaps.

It's worth noting that this paper mentions the word

• "metabolism" - 20 times
• "metabolic" - 4 times
• "homeostasis" - 3 times (1x in intro, 1x in methods, 1x in references)

The word "homeostasis didn't even enter my mind to look for. When I look now in Protege, I don't see any connection between glucose homeostasis and either glucose metabolic process or regulation of glucose metabolic process. Considering that my initial search was for regulation of glucose metabolic process in order to see what was there and try to find what was most appropriate, it seems like a failing that I did not find glucose homeostasis.

I also think 'metabolic process' is not really useful as an annotation, if we dont know whether a protein is involved in synthesizing or degrading a compound then we should probably not annotate it. And regulation is even more indirect.

The annotations I made are:

• insulin receptor signaling pathway (GO:0008286) acts upstream of or within regulation of glucose metabolic process (GO:0010906)
• negative regulation of gluconeogenesis (GO:0045721) occurs in liver (EMAPA:16846)

To discuss on a call ?

If you like.

[thomaspd]

Like for other BP terms, we should think about the biological program that "negative regulation of glucose metabolic process" would describe. I tend to think of the negative and positive regulatory programs being tightly coupled, so maybe glucose homeostasis is the more useful class for the GO biological program.

The way the term is being used now, are curators trying to say that a gene product's activity has a negative causal effect on glucose metabolism? That would be a good use case for our gp2term relationship-- a curator could annotate to "glucose metabolic process" using the "acts causally upstream of, negative effect" relation.

[deustp01]

The way the term is being used now, are curators trying to say that a gene product's activity has a negative causal effect on glucose metabolism?

Jumping in from left field, "glucose metabolism" seems like a grouping term for really diverse processes (glycolysis and gluconeogenesis, for a start, as well as all the other processes in Karen's list at the top of this ticket) that have diverse, physiological state-specific, tissue-specific, and taxon specific roles in an organism's energy economy, so should "(positive OR negative) regulation of glucose metabolic process" likewise be a grouping term, useful for collecting all of these processes into a single bucket but not normally useful for annotating the roles of specific gene products in specific processes. On this grouping view, Paul's question has as many diverse answers as there are diverse processes / states / tissues / organisms. @ukemi ?

[krchristie]

Like for other BP terms, we should think about the biological program that "negative regulation of glucose metabolic process" would describe. I tend to think of the negative and positive regulatory programs being tightly coupled, so maybe glucose homeostasis is the more useful class for the GO biological program.

The way the term is being used now, are curators trying to say that a gene product's activity has a negative causal effect on glucose metabolism? That would be a good use case for our gp2term relationship-- a curator could annotate to "glucose metabolic process" using the "acts causally upstream of, negative effect" relation.

I think this is a reasonable question, but I should point out that there is not currently a negative regulation of glucose metabolism term, as the point of the ticket is the inconsistency due to the lack of this term.

It's also worth pointing out that for the regulation of glycogen metabolic process set of terms, both the positive and negative regulation terms already exist, (though neither has annotations).

I agree that you have a good question Paul as I have made annotations to a "plain" regulation term many times when it is not clear to me what the positive or negative direction would actually mean. However, it seems that the question of exactly what one would be trying to say applies equally to the existing term positive regulation of glucose metabolic process which already exists and has annotations, including experimental ones.

Looking above at the existing glycogen regulation terms, one can ask what the directional regulation of metabolic process terms mean when negative regulation of a biosynthetic process and negative regulation of a catabolic process would have opposite effects on levels of the metabolized compound.

To bring it back to this specific question, it seems that we should either follow the consistent structure of regulation terms that we have had elsewhere and add the missing negative regulation of glucose metabolic process term, or we should not have the existing positive regulation of glucose metabolic process term. If we choose the latter course, this is likely only the tip of the iceberg of similar terms as we have been building this consistent type of structure of regulation terms for years.

Here are the child terms of regulation of glucose metabolic process along with annotation counts of terms that have been used.