Missing parent: membrane lipid biosynthetic process (GO:0046467)

[ValWood]

• GO term ID and label for which you request a new superclass

membrane lipid biosynthetic process (GO:0046467)

• New superclass (parent) suggested

Add parent membrane biogenesis GO:0044091

[pgaudet]

Should we obsolete this term? Or are membrane lipids synthesized differently from other lipids ?

[ValWood]

I'm not sure. I guess only some classes of lipids are part_of membranes

So, the lipids which are membrane components are listed under here, so that they appear as part of membrane organization (ceramide, sphingolipid etc)

Others are storage like triglycerides and waxes or signalling (steroids excluding cholesterol). I feel it could be useful to include many annotations under membrane biogenesis without needing to make a concurrent annotation in every case.

[deustp01]

I'm not sure. I guess only some classes of lipids are part_of membranes

Is this a part_of / capable_of issue? I do not in fact understand how this particular bit of logic works, only that it exists, people use it, and it may be applicable here. I wonder, for a lipid's biosynthesis to fit under membrane lipid biosynthetic process (GO:0046467), is it enough for some of that class of lipid to be localized to membranes under at least some conditions, or must membrane localization be the only possible fate of the lipid class for it to qualify? If it's the second, very few will qualify.

[ValWood]

I wonder, for a lipid's biosynthesis to fit under membrane lipid biosynthetic process (GO:0046467), is it enough for some of that class of lipid to be localized to membranes under at least some conditions, or must membrane localization be the only possible fate of the lipid class for it to qualify?

I have never fully understood this either. Maybe a question for an ontology call.

[pgaudet]

only some classes of lipids are part_of membranes

but are these only present in membranes? see https://en.wikipedia.org/wiki/Phosphatidylglycerol (from https://github.com/geneontology/go-ontology/issues/26699)

The term 'membrane lipid biosynthetic process' makes classification difficult, because we need to identify lipids that are only in membranes. I am not sure this would be a useful grouping term, since it could not contain ALL membrane lipids (or else that would cause a TPV).

[deustp01]

I can't think of any lipid whose exclusive fate is membrane localization. For example, cholesterol is a prominent membrane component but also consumed for the production of steroid hormones, bile acids, and vitamin D. Fatty acids, incorporated into triglycerides, are prominent membrane components, but are also stored (as triglycerides) for catabolism and energy generation when exogenous nutrient supplies are low. and so on. And the lipid contents of lipoprotein particles can be extracted by cells and directed into cellular membranes but they can also be directed into metabolic processes without ever becoming a part of a cell membrane. Maybe phosphatidylglycerols would fit into the only-ever-in-membrane class? Is it useful biology to classify membrane lipids according to whether they can also function elsewhere, especially if almost all can do so? @kaxelsen @sjm41 ?

[ValWood]

It doesn't really make sense to say that various lipid synthesis are part of specific membrane organization, really it would be 'causally upstream' because the synthesis occurs in the ER (mainly) and them membranes are trafficked to other destinations.

So I can go with @pgaudet suggestion to obsolete "membrane lipid biosynthetic process (GO:0046467)" This probably means that membrane organization lipid biosynthesis should be disjoint

We would also need to look at GO:0071709 membrane assembly The aggregation, arrangement and bonding together of a set of components to form a membrane.

and descendants for example GO:0032120 ascospore-type prospore membrane formation GO:0097104 postsynaptic membrane assembly GO:0001765 membrane raft assembly to see if they are about lipid synthesis, or reorganization of existing membranes, in which "membrane reorganization" might be more appropriate than assembly (seems to be a mixture)

[pgaudet]

Hi @ValWood

It would be useful to consider this globally - this is not the only place in the ontology where we have issues with biosynthesis, organization and biogenesis.

Also, when you look at metabolic terms, please remember to look at the entire triad: we also have GO:0006643 membrane lipid metabolic process and GO:0046466 membrane lipid catabolic process, plus GO:1905038 regulation of membrane lipid metabolic process. Usually, we'll want to remove all these terms.

Thanks, Pascale

[ValWood]

It would be useful to consider this globally - this is not the only place in the ontology where we have issues with biosynthesis, organization and biogenesis.

I'm not sure that one size will fit all, it depends somewhat on biology and community usage

[deustp01]

It would be useful to consider this globally

I wonder if cassettes would be useful here, as they are for long and complicated signalling processes. By default, a metabolic process draws from a cellular pool of input molecule and contributes to a cellular pool of output molecule, without tagging those molecules to identify their ultimate use. Thus the process that makes cholesterol has no way of designating a particular cholesterol molecule for vitamin D synthesis or delivery to a membrane to function as a structural element. Cassettes in a GO-CAM framework can handle these long-range activity flows.

I imagine items like membrane lipid biosynthesis are really useful in a pre-GO-CAM world; now we no longer need them (though building their replacements is a major chore, so we can't just dump them unless there are resources to build replacements).

Is this useful / sensible? @sjm41 @ukemi

[ValWood]

I think what you are suggesting here is along the lines I had planned to do for PomBase.

I haven't been using the "causally upstream" relationship, only part of, but obviously we want to connect pathways together when one pathway is necessarily upstream of another.

The "causally upstream" relation doesn't seem a very scalable way to do this, but I have been making notes of the upstream downstream relationships between pathways, so eventually they can be connected.

For example fatty acid synthesis is required for nuclear membrane reassembly, but not part of it. I can connect instead fatty acid synthesis -causally upstream- nuclear membrane reassembly

This seems to be more efficient than making lots of independent causally upstream connections between individual gene products and it keeps the GOCAM models modular. I guess this is the same approach as "cassettes". This is just to let you know I'm collecting the info about the relationships between modules (although I guess a lot of this is already available via Reactome?)

[pgaudet]

Let's go ahead with obsoletion of: GO:0006643 membrane lipid metabolic process >> replace by GO:0006629 lipid metabolic process GO:0046467 membrane lipid biosynthetic process >> replace by GO:0008610 lipid biosynthetic process GO:0046466 membrane lipid catabolic process >> replace by GO:0016042 lipid catabolic process GO:1905038 regulation of membrane lipid metabolic process >> replace by GO:0019216 regulation of lipid metabolic process

Looking at QuickGO there are less than 10 direct annotations to these terms.

Thanks, Pascale