missing parent: GO:0038187 pattern recognition receptor activity

[ValWood]

GO:0038187 pattern recognition receptor activity Definition Combining with a pathogen-associated molecular pattern (PAMP), a structure conserved among microbial species, or damage-associated molecular pattern (DAMP), an endogenous molecule released from host damaged cells, to initiate an innate immune response.

should be a descendant of GO:0140376 innate immune receptor activity

[ukemi]

@addiehl?

[ValWood]

or the definition would need to be fixed: "to initiate an innate immune response"

(DAMPS should not be lumped in here, they were added recently, but they are inflammatory response. There is another ticket about this assigned to @pgaudet

[pgaudet]

@ValWood I changed all defs to remove 'damage-associated molecular pattern (DAMP)' - can you check ?

[addiehl]

I think the original definition is correct per the literature (not wikipedia):

Per PMID:31736963: Much has been focused on host response to pathogens mediated through the interaction of pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs). PRRs are also activated by host nuclear, mitochondrial, and cytosolic proteins, known as damage-associated molecular patterns (DAMPs) that are released from cells during sepsis.

Per PMID:31558839: Although the danger theory generated much enthusiasm and has provoked multiple controversies over the past 20 years (see also Box 1), it is now largely accepted that both PAMPs and DAMPs can initiate immune responses through the activation of classical PRRs, which include not only TLRs but also multiple germ-line-encoded receptors, such as NOD-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs) and multiple intracellular DNA sensors.

Per PMID: 30309020: These danger- or death-associated molecular patterns (DAMPs) resemble a quite diverse group of discompartmentalized molecules. They comprise nucleic acids in various conformations (e.g., single-/double-stranded (ss/ds) RNA or DNA), nuclear proteins (e.g., high mobility group box-1, HMGB-1), cytosolic proteins (e.g., keratin-18, K18), purine nucleotides (e.g., adenosine triphosphate, ATP), or mitochondrial compounds (e.g., mtDNA, N-formyl peptides), among others. Being sensed by evolutionary conserved pattern recognition receptors (PRRs) [4] within the cytosol, as by nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) or retinoic acid-inducible gene (RIG)-1-like receptors (RLRs), or from the outside by membranous Toll-like receptors (TLRs) or the receptor for advanced glycation end products (RAGE), DAMPs alert innate immunity responses.

PAMPs and DAMPs often bind to the same PRRs, so it is appropriate to use GO:0038187 pattern recognition receptor activity for both.

I don't think the parentage should be changed, as both PAMPs and DAMPs drive inflammatory processes and while PAMPs specifically promote innate immune responses via the influx of immune cell types in that inflammatory response, DAMPs also can promote innate immune responses when a pathogen is present by driving an influx of immune cell types in an inflammatory response. In the absence of a pathogen, so called "sterile inflammation" occurs, where those immune cell types promote symptoms of inflammation like edema and non-specific tissue damage.

[ukemi]

Thanks @addiehl

[ValWood]

In this case we would need to fix the definition, and remove from "immune receptor activity" or create immune specific receptor terms.

It makes sense for @pgaudet to do this as it impacts some other tickets.

[ValWood]

So based on @addiehl comments we need to add DAMPs back to "GO:0038187 pattern recognition receptor activity"

However, the processes we are annotating at PHI base are immune system specific processes and so we would like immune system-specific terms for these. I will update the other tickets accordingly based on the curation output we require and taking into accounts @addiehl comments about DAMPs

[ValWood]

@pgaudet the editing comments are appearing here: https://www.ebi.ac.uk/QuickGO/term/GO:0038187

this appears to be a new thing? Merged terms, edited definiton and synonyms, see https://github.com/geneontology/go-ontology/issues/17995. Removed DAMP from the definition and synonyms, as this is a different process, see https://github.com/geneontology/go-ontology/issues/18588.

At least historically these comments used to be for useage guidelines, not for ontology edits?

[ValWood]

One downside is that PRR receptor will NEVER be classed as "immune receptors" by this schema. All of the ones annotated so far are "immune receptors" so I will require a child term to get this classification.

GO:xxxxxNTR MAMP/PAMP receptor activity This would have the recent definition for GO:0038187 pattern recognition receptor activity i.e. Combining with a pathogen-associated molecular pattern (PAMP), a structure conserved among microbial species to initiate an innate immune response. (and the "narrow synonyms" can be removed from GO:0038187)

That would solve my problems.

[addiehl]

Child terms seem appropriate to me.