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jhuapl-bio / pathogenesis-gene-ontology

An ontology for the functional annotation of genes and gene products involved in pathogenesis
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Disrupting toll-like receptor signaling--notes on annotation #166

Open genegodbold opened 3 years ago

genegodbold commented 3 years ago

So this maybe just an FYI for these entities: PATHGO_0000103 (host toll-like receptor signaling disruption factor) AND PATHGO_0000233 (disrupts host toll-like receptor signaling). This is related to issue #211.

There are dozens of these things in bacteria alone, particularly in the genus Mycobacterium. In my annotations I have been including proteins that:

  1. Agonize toll-like receptors
  2. Antagonize toll-like receptors
  3. Interfere with intracelllular toll-like receptor signaling at the level of MyD88 or above (there are a few proteins that specifically interact with MyD88 to inhibit TLR signaling in the cell including: BtpA and BtpB from various Brucellae, TcpC from E. coli, TcpS from Salmonella, and maybe TlyA from M. tuberculosis).

Eventually we might want to distinguish the ones that are acting intracellularly versus the ones that are binding to the receptors extracellularly. Also, there may eventually be enough annotated to justify specifying which toll-like receptor is involved (TLR2 and TLR4 are the ones that seem to be getting hit the most often).

Attribution

https://orcid.org/0000-0002-5702-4690

jacakrj1 commented 3 years ago

Added these notes to the editorialNote on the 'disrupts host toll-like receptor signaling'. I think the 'agonist' and 'antagonist' concepts may be covered by the GO terms "GO:0034123 positive regulation of toll-like receptor signaling pathway" and "GO:0034122 negative regulation of toll-like receptor signaling pathway". Thoughts?

genegodbold commented 3 years ago

Yes, but those terms (GO:0034123 and GO:0034122) are going to be "contaminated" with normal agonism/antagonism processes. The PATHGO term is for exogenous (non-native) modulation. And not passive (LPS binding to TLR4) but active. Is there a way to capture that sort of thing? Also, those GO terms are nonspecific for where in the pathway the action occurs. I would want to make clear that this comes from binding to the receptor itself and not by messing with anything downstream.