Abnormal T cell subtype distribution

[pnrobinson]

Related #2396 #2436 #2445 #2461

Let's start with a list of the t cell subtypes and start to add the markers as synonyms.

[pnrobinson]

Please if you choose a cell to work on, add it here:

• Memory T cell [Peter]
• Naive T cell [Nicole]
• Helper T cell [Leigh]
• xyz
• xyz

[nicolevasilevsky]

This is the T cell hierarchy in CL:

T cell

• alpha-beta T cell
• gamma-delta T cell
• immature T cell
  • immature alpha-beta T cell
  • immature gamma-delta T cell
  • thymocyte
• mature T cell
  • effector T cell: effector cells are CD45RA+CD45RO–CCR7–CD62L– (ref*)
  • intraepithelial lymphocyte
  • mature alphta-beta T cell
  • memory T cell
    • CD4-positive, alpha-beta memory T cell
      • central memory CD4-positive, alpha-beta T cell: central memory T cells are CD45RA- CD45RA–CD45RO+CCR7+CD62L+ (ref)
      • effector memory CD4-positive, alpha-beta T cell: effector memory T cells are CD45RA–CD45RO+CCR7–CD62L– (ref)
    • CD8-positive, alpha-beta memory T cell
      • central memory CD8-positive, alpha-beta T cell
      • effector memory CD8-positive, alpha-beta T cell
  • naive T cell: Naïve CD4 and CD8 T cells are CD45RA+CD45RO–CCR7+CD62L+ (ref)
  • regulatory T cell

*this reference is to a blog, this article describes naive and memory T cell phenotypes too: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1782715/

This article (PMC4810120) has a nice figure (see below):

[LCCarmody]

Are we doing all these cells? And abnormal count and activation? It is hard to tell jumping from ticket to ticket. In any event, it was decided to use CL for the hierarchy. We would need to MIREOT the following if we plan to do all those listed. * gamma-delta T cell

• gamma-delta T cell | http://purl.obolibrary.org/obo/CL_0000798
• CD4-positive, alpha-beta memory T cell | http://purl.obolibrary.org/obo/CL_0000897
• immature gamma-delta T cell | http://purl.obolibrary.org/obo/CL_0000799
• intraepithelial lymphocyte | http://purl.obolibrary.org/obo/CL_0002496
• central memory CD4-positive, alpha-beta T cell | http://purl.obolibrary.org/obo/CL_0000904
• effector memory CD4-positive, alpha-beta T cell | http://purl.obolibrary.org/obo/CL_0000905
• CD8-positive, alpha-beta memory T cell | http://purl.obolibrary.org/obo/CL_0000909
• central memory CD8-positive, alpha-beta T cell | http://purl.obolibrary.org/obo/CL_0000907
• effector memory CD8-positive, alpha-beta T cell | http://purl.obolibrary.org/obo/CL_0000913

[drseb]

can you give me the purls or ids of the classes to mireot?

[LCCarmody]

@drseb Updated above and listed below. Wasn't sure which was better.

http://purl.obolibrary.org/obo/CL_0000798
http://purl.obolibrary.org/obo/CL_0000897
http://purl.obolibrary.org/obo/CL_0000799
http://purl.obolibrary.org/obo/CL_0002496
http://purl.obolibrary.org/obo/CL_0000904
http://purl.obolibrary.org/obo/CL_0000905
http://purl.obolibrary.org/obo/CL_0000909
http://purl.obolibrary.org/obo/CL_0000907
http://purl.obolibrary.org/obo/CL_0000913

[drseb]

currently having problems regenerating cl_import due to internet connection problems. please remind me if forget to re-run this later

[drseb]

sorry. regenerating cl_import currently does not change the cl-import. need help from @matentzn

[nicolevasilevsky]

Do we want to add logical definitions for terms that are 'abnormal proportion fo [cell type]? I don't think we have a pattern for that, and I am not sure how to write the logical def.

[pnrobinson]

Note that the pattern should include the numerator and denominator, and we will likely have to adjust some according to feedback. i.e., the proportion with respect to X cell type can be different.

[nicolevasilevsky]

I added new terms:
Abnormal/increased/decreased proportion of CD4 and CD8-positive, alpha-beta memory T cells
and
Abnormal/increased/decreased proportion of CD4 and CD8-positive, alpha-beta effector and central memory T cells

as children of HP_0032182 'Abnormal proportion of memory T cells'

[pnrobinson]

I added a few more terms. At this point, I think we really need to see if we are going in the right direction and get some feedback from the immunologists as to what is missing and whether the proportions (denominator) are correct. Let's hold off on this until we get more feedback. I would even close this term and make individual issues for the cell types, these mega issues are really hard to deal with> @nicolevasilevsky

[pnrobinson]

@nicolevasilevsky Can we touch bases about this and try to close this issue?

[nicolevasilevsky]

sure! Did you you get any feedback from the immunologists?

[pnrobinson]

@nicolevasilevsky @LCCarmody I think it would be good to add terms for the cell types listed in Leigh's message above, but not for intraepithelial lymphocyte, which is not circulating. Can we touch bases to coordinate this?

[nicolevasilevsky]

Yes, do you want to set up a meeting @pnrobinson?

[pnrobinson]

@LCCarmody @nicolevasilevsky could we meet this week to work on this?

[nicolevasilevsky]

Per the call today, here are our action items:

• Nicole: request new terms to PATO: increased proportion, decreased proportion
• Nicole: create patterns in uPheno for: abnormalProportionOfCellTypeInAnatomicalEntity, decreasedProportionOfCellTypeInAnatomicalEntity, increasedProportionOfCellTypeInAnatomicalEntity
  (Note- this is dependent on the new PATO terms above)
• @LCCarmody and Nicole: need a list of all the cell types that should be added to HPO via the DOSDP
• @LCCarmody and Nicole: coordinate with @matentzn to add these new terms to HPO

[matentzn]

Nice one!

[nicolevasilevsky]

@pnrobinson @LCCarmody
cc @matentzn and @dosumis

@matentzn and @dosumis - On a call today with @pnrobinson and @LCCarmody, we decided we needed a pattern for:
Abnormal T cell proportion
Increased T cell proportion
Decreased T cell proportion

I suggested this pattern:
text: "'has_part' some ('proportionality to' and ('inheres_in' some (%s and ('part_of' some %s))) and ('has_modifier' some 'abnormal'))"
vars:

• cell
• location

@matentzn commented:
This sounds like a relational quality... Proportionality compared to what? All other cell types in the location?

We decided our call that we didn't want to state that the abnormal (or increased or decreased) proportion was relative to other cells. Do we need to have that in order to use this quality?

@pnrobinson would you mind explaining the rationale for that?

[LCCarmody]

I'm linking a google doc collected just from terms that are listed as 'proportional' in HP. Most are straight forward and have a relational quality listed in the text definition (ie. proportional to B cells or T cells). A few aren't stated.

There are a number of cells I can't find terms that match in CL. EIther it is too vague or I think it is a duplicate. HP hasn't been consistent with naming or location of these terms, so I suspect a number of terms are redundant and need to be merged, but I am not absolutely positive. In particular, most of these terms are listed under abnormal T cell distribution, but many are listed directly under decreased/increased count of some cell type.
@pnrobinson @nicolevasilevsky Could you look to see if some of these terms are the same? I used the notes section to suggest which I thought were the same.

[nicolevasilevsky]

From Huddle:
Peter said we should use functional cell terms from the CL
Add to comments in HPO - this combination of markers is used to measure cells

We should make individual issues for terms where we have questions and we can share with the immunologists

[nicolevasilevsky]

• @nicolevasilevsky and @LCCarmody- we should create a ticket for each term (see google doc above), and @pnrobinson will try to find PMIDs for each term.

[pnrobinson]

done