PhiBabs935
commented
4 years ago One general note: After seeing Oliver's figure 5 from (https://arxiv.org/ftp/arxiv/papers/2006/2006.00639.pdf) I realize that RO has more specific relations we could use in various axioms. I will have to look through RO again carefully for the relevant relations (e.g. 'activates', 'induces' 'stimulates' etc).
Still working on this In this issue I will compile terms for inclusion (either imported or newly created) in VIDO pertaining to immune responses. I also suggest viral immune response specific axioms to connect the imported terms.
Import from GO
GO provides many relevant subclasses of innate immune response (GO term already in IDO Core and VIDO):
antiviral innate immune response http://purl.obolibrary.org/obo/GO_0140374 virus induced gene silencing http://purl.obolibrary.org/obo/GO_0009616 and its children, RNA virus induced gene silencing and DNA virus induced gene silencing
*RNA virus induced gene silencing is commonly just called "RNA silencing".
the role of interferons in viral immunology from Introduction to Modern Virology (IMV):
interferons block virus multiplication: so we should add to interferon the axiom: has disposition some virostatic disposition
interferons "upregulate [positively regulate] expression of MHC I proteins, enhancing the antiviral activity of T cells by increasing the concentration of foreign peptides presented on the cell surface..." The upregulation of MHC I proteins increases antiviral activity by enhancing the presentation of MHC I dependent antigens. In virtue of upregulating the expression of MHC I proteins, interferons upregulate antigen presentation. -as for gene expression (synthesis) of MHC I proteins, I believe the relevant term to import would be: GO:MHC class I biosynthetic process =def The chemical reactions and pathways resulting in the formation of major histocompatibility protein class I.
Thus, for whatever term we use for interferons, we can add the axiom: positively regulates some MHC class I biosynthetic process
And for the upregulation of antigen presentation this facilitates: positively regulates some GO: antigen processing and presentation
Update 6/23: Looking at GO more closely, I believe that we can actually capture "upregulate [positively regulate] expression of MHC I proteins, enhancing the antiviral activity of T cells by increasing the concentration of foreign peptides presented on the cell surface..." precisely using the following GO subclass of antigen processing and presentation:
antigen processing and presentation of peptide antigen via MHC class I =def The process in which an antigen-presenting cell expresses a peptide antigen on its cell surface in association with an MHC class I protein complex. Class I here refers to classical class I molecules. [http://purl.obolibrary.org/obo/GO_0002474] ***plus this class has lots of specific subclasses, but I would have to study them more carefully
So we can add the axiom: interferon positively regulates some antigen processing and presentation of peptide antigen via MHC class I -Does that sound right to you? I thought this would capture the notion that interferons help to facilitate an increase in the concentration of foreign (antigen) peptides.
Then, could we add an axiom that expresses the causal relation between antigen processing and presentation of peptide antigen via MHC class I and the antiviral activity of T cells, for instance:
antigen processing and presentation of peptide antigen via MHC class I [insert an appropriate ontology term that captures the meaning of 'enhances' in the quote from IMV above] GO: T cell mediated immunity (Any process involved in the carrying out of an immune response by a T cell). *Of course, we would want axioms involving virus specific subclasses of GO: T cell mediated immunity [will have to look more closely to find relevant ones here: https://www.ebi.ac.uk/ols/ontologies/go/terms?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2FGO_0002456]
Also, we could add that interferon participates in some positive regulation of MHC class I biosynthetic process (the latter is a GO term that is equivalent to: biological process and positively regulates some MHC class I biosynthetic process)
Interferon secretion and production Interferons are secreted by cells in response to virus infection. Here we can import for type I interferons: GO: type I interferon secretion =def The regulated release of type I interferon from a cell. [http://purl.obolibrary.org/obo/GO_0072641]; but also imports its subclasses for specific interferons (alpha/beta, etc) -This class has the axiom: part of some type I interferon production Thus we should import: GO: type I interferon production = def The appearance of type I interferon due to biosynthesis or secretion following a cellular stimulus, resulting in an increase in its intracellular or extracellular levels. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.
As for gamma (type II) interferons: GO: interferon-gamma secretion Which is part of some interferon-gamma production
-Processes leading to interferon secretion Interferon production is triggered when the molecules within microbes (including viral RNA and viral glycoproteins) bind with pattern recognition receptors (PPRs), such as Toll receptors. PPRs recognize and bind with pathogen-associated molecular patterns (PAMPS). I am not sure about this completely, but I think that this sort of interferon production has to do with type I interferons which are secreted from virus infected cells. -Type I interferons can be induced in virtually all cell-types, upon recognition of viral components by the cell. -I think we can import the following GO term for the above: GO: pattern recognition receptor activity =def Combining with a pathogen-associated molecular pattern (PAMP), a structure conserved among microbial species to initiate an innate immune response. [http://purl.obolibrary.org/obo/GO_0038187], though we might clean this textual definition up for VIDO... **Should we add or request for virus specific subclasses of this process?
Suggested axiom: pattern recognition receptor activity positively regulates some type I interferon secretion **Not sure: I know there is a causal relation here, but is it right to use positively regulates?
I was thinking of an axiom: capable of type I interferon secretion -Would this be asserted of all cells whatsoever? Any cell has the capability to secrete them, upon being infected?
interferon-gamma secretion is more specific: the secretion of interferon-gamma is restricted to immune cells such as T cells, natural killer cells and macrophages. -So I would add the following axiom for each of these cell classes (which we will import into IDO Core from the Cell Ontology--see IDO Core issue #10): capable of interferon gamma secretion
interferon gamma production is induced by cytokines such as various types of interleukins. If we import relevant classes from the Protein ontology (such as PRO: interleukin-1), would we give them axioms like?:
Type II, or gamma-interferons, can activate both natural kill cells and macrophages during immune response: -Suggested related axioms: capable of some macrophage activation involved in immune response [latter term is from GO -> http://purl.obolibrary.org/obo/GO_0002281] capable of some natural killer cell activation involved in immune response [latter term is from GO]
Interferon binding: UPDATE 6/30--I need to clean up the following “Receptor binding by all interferons stimulates cellular transcription which results in antiviral activity and upregulation of MHC proteins.” (IMV, p. 199) For interferon receptor binding I think* we can import GO: interferon binding [http://purl.obolibrary.org/obo/GO_0019961]; we can also import its subclasses, such as type I interferon binding and interferon-gamma binding Actually, maybe not, see below
UPDATE 6/30 We have to be careful about the GO terms we import for the purpose of representing interferons and the JAK-STAT pathway. The JAK-STAT pathway is activated by the binding of cytokines to cell receptors on the cell surface. GO: has two slightly different classes:
GO: cytokine binding =def Interacting selectively and non-covalently with a cytokine, any of a group of proteins that function to control the survival, growth and differentiation of tissues and cells, and which have autocrine and paracrine activity.
GO: cytokine receptor binding =def Interacting selectively and non-covalently with a cytokine receptor. (subclass of signaling receptor binding)
I am not actually sure which one is relevant for our purposes. One the one hand, GO: cytokine binding is part of GO: cytokine receptor activity, and the latter is a subclass of GO: immune receptor activity and is part of a GO: cytokine-mediated signaling pathway
But cytokine receptor binding also seems relevant, as the binding of cytokine (e.g. interferon, interleukin) to a cell receptor is part of the immune response.
UPDATE 7/1 As I noted above, GO: cytokine receptor activity is part of some GO: cytokine-mediated signaling pathway. The latter class is a GO: Cell surface receptor signaling pathway. One of cytokine-mediated signaling pathway's sibling classes is receptor signaling pathway via STAT, which itself is the parent of receptor signaling pathway via JAK-STAT (the GO class for JAK-STAT signaling pathways).
Some receptor signaling pathways via JAK-STAT are cytokine-mediated signaling pathways (those initiated by the binding of cytokines to cell receptors). This suggests that GO: cytokine binding (which is part of some cytokine receptor activity, and therefore part of some cytokine-mediated signaling ) is the correct term to use for the initial stage of JAK-STAT pathways that are initiated by the binding of cytokines to cell receptors. [And in the pathways initiated by interferons in particular, GO: interferon binding
This still leaves me wondering what the role of the GO class cytokine receptor binding is supposed to be. There are no axioms or is a relations connecting this class to either GO: cytokine receptor activity or cytokine binding even though the definition of cytokine receptor binding suggests there is a link. end update
Note that cytokine binding has GO: interferon binding as a subclass, which in turn has the subclasses: interferon-gamma binding, type III interferon binding, type I interferon binding)
cytokine receptor binding has the following subclasses, among many others: interferon-gamma receptor binding and type I interferon receptor binding. *Notice that there is no type III interferon receptor binding class. This is surprising, as type III interferons also signal through cell receptors.
The rest of this needs to be cleaned up still; will do so once I finish compiling the relevant GO process classes -Notice that the positive regulation of MHC synthesis is part of a bigger process, so should we create a term for the whole process? -The binding of interferons to cell receptors stimulates cellular transcription, usually just called transcription, the process of making an RNA copy of a gene sequence, i.e. a messenger RNA (mRNA). So, for cellular transcription we would import: GO: mRNA transcription [http://purl.obolibrary.org/obo/GO_0009299] -I am pretty sure that 'activation' or 'stimulation' of molecular activity falls under RO: positively regulates. So we could add the following axiom for interferon binding: interferon binding positively regulates mRNA transcription
Any ideas for axioms to connect the above processes together?
Related to interferon binding ... GO: interferon receptor activity -In GO it is asserted interferon receptor activity has part some interferon binding interferon receptor activity is defined as: “Combining with an interferon and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity.” [http://purl.obolibrary.org/obo/GO_0004904]
interferon receptor activity has subclasses we should also import: interferon-gamma receptor activity, type I interferon receptor activity and type III interferon receptor activity (the same part-whole relations hold between these and the subclasses of interferon binding)
Issue: is it specifically the interferon binding part of the process that stimulates cellular transcription? Or is it interferon binding and the receptor activity together which stimulate it?
We might also incorporate from GO the connect between interferon receptor activity and cell communication. See: https://www.ebi.ac.uk/ols/ontologies/go/terms?iri=http://purl.obolibrary.org/obo/GO_0004904 -Incorporating this captures the fact that interferons send signals to other nearby cells to heighten their antiviral defenses.