Difference between revisions of "Annotation Conf. Call 2016-10-25"

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(Annotation Consistency Exercise)
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| ferritin
 
| ferritin
 
| ferric ion import GO:0033216
 
| ferric ion import GO:0033216
| ?
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| IDA
 
| SGD
 
| SGD
 
|occurs_in UBERON:0000320 duodenal mucosa
 
|occurs_in UBERON:0000320 duodenal mucosa
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| Tf, transferrin
 
| Tf, transferrin
 
| ferric ion import GO:0033216
 
| ferric ion import GO:0033216
| ?
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| IDA
 
| SGD
 
| SGD
 
|occurs_in UBERON:0000320 duodenal mucosa
 
|occurs_in UBERON:0000320 duodenal mucosa

Revision as of 16:55, 25 October 2016

Bluejeans URL: https://bluejeans.com/993661940

Agenda

Meetings

Next GOC Meeting - USC, Los Angeles, CA, November 4-6, 2016

  • Link to a registration form is now available for the USC Meeting on the Meeting Logistics Page.
  • Register for meeting and dinner, just dinner, just meeting.
  • No registration fee for the Noctua workshop.
  • Draft Agenda - please review

Discussion of Outstanding github Tickets

Annotation Consistency Exercise

Abstract AIM:To elucidate the sequential transfer of iron amongst ferritin, transferrin and transferrin receptor under various iron status conditions. METHODS:Incorporation of 59Fe into mucosal and luminal proteins was carried out in control WKY rats. The sequential transfer of iron amongst ferritin, transferrin and transferrin receptor was carried out in iron deficient, control and iron overloaded rats. The duodenal proteins were subjected to immunoprecipitation and quantitation by specific ELISA and in situ localization by microautoradiography and immunohistochemistry in tandem duodenal sections. Human duodenal biopsy (n = 36) collected from subjects with differing iron status were also stained for these proteins. RESULTS:Ferritin was identified as the major protein that incorporated iron in a time-dependent manner in the duodenal mucosa. The concentration of mucosal ferritin was significantly higher in the iron excess group compared to control, iron deficient groups (731.5 +/- 191.96 vs 308.3 +/- 123.36, 731.5 +/- 191.96 vs 256.0 +/- 1.19, P < 0.005), while that of luminal transferrin which was significantly higher than the mucosal did not differ among the groups (10.9 +/- 7.6 vs 0.87 +/- 0.79, 11.1 +/- 10.3 vs 0.80 +/- 1.20, 6.8 +/- 4.7 vs 0.61 +/- 0.63, P < 0.001). In situ grading of proteins and iron, and their superimposition, suggested the occurrence of a sequential transfer of iron. This was demonstrated to occur through the initial binding of iron to luminal transferrin then to absorptive cell surface transferrin receptors. The staining intensity of these proteins varied according to the iron nutrition in humans, with intense staining of transferrin receptor observed in iron deficient subjects. CONCLUSION:It is concluded that the intestine takes up iron through a sequential transfer involving interaction of luminal transferrin, transferrin-transferrin receptor and ferritin.

Discussion Points

  1. What can be done with ferritin annotations, since a specific subunit was non identified in the paper?
  2. Should colocalization (IEP) data be used for biological process annotations?
  3. If an iron transport annotation is made, does an iron homeostasis annotation impart any additional information?
  4. Is "intestinal absorption" too broad? Should an intestinal iron absorption term be requested?

Accompanying LEGO Model

Annotations

Gene Symbol, Gene Name GO term/ID Evidence Code Annotation Source Annotation Extension Comment
Biological Process
ferritin iron ion transport GO:0006826 IDA FB, Tair Which ferritin subunit?
Tf, transferrin iron ion transport GO:0006826 IDA FB, Tair transport is inferred from radioactive Fe sequential colocalizing with location of each of the proteins in different parts of the duodenum
Tfrc, transferrin receptor iron ion transport GO:0006826 IDA FB, Tair Tfrc or Tfr2?
Tf, transferrin ferric iron transport GO:0015682 IDA RGD
ferritin ferric ion import GO:0033216 IDA SGD occurs_in UBERON:0000320 duodenal mucosa
Tf, transferrin ferric ion import GO:0033216 IDA SGD occurs_in UBERON:0000320 duodenal mucosa
Tf, transferrin GO:0098706 -ferric iron import across plasma membrane IEP WB
Tfrc, transferrin receptor GO:0098706 -ferric iron import across plasma membrane IEP WB
ferritin iron ion homeostasis GO:0055072 IDA FB Which ferritin subunit?
Tf, transferrin iron ion homeostasis GO:0055072 IDA FB transport is inferred from radioactive Fe sequential colocalizing with location of each of the proteins in different parts of the duodenum
Tfrc, transferrin receptor iron ion homeostasis GO:0055072 IDA FB
ferritin, Fth1, Ftl1 GO:0060586 - multicellular organismal iron ion homeostasis IEP WB occurs_in(UBERON:0016512) lumen of duodenum
Tf, transferrin GO:0060586 - multicellular organismal iron ion homeostasis IEP WB occurs_in(UBERON:0016512)lumen of duodenum
Tfrc, transferrin receptor GO:0060586 - multicellular organismal iron ion homeostasis IEP WB occurs_in(UBERON:0002114) duodenum
Tf, transferrin GO:0050892 - intestinal absorption IEP WB has_input(ChEBI:29034) Maybe request "intestinal iron ion absorption".
Tfrc, transferrin receptor GO:0050892 - intestinal absorption IEP WB has_input(ChEBI:29034)
Tf, transferrin response to iron ion GO:0010039 IEP RGD movement between compartments dependent on iron level in diet
Tfrc, transferrin receptor response to iron ion GO:0010039 IEP RGD
human ferritin, FTH1 (UniProtKB:P02794), FTL (UniProtKB:P02792) GO:0060586 - multicellular organismal iron ion homeostasis IEP WB occurs_in(UBERON:0002114) duodenum
human TF (UniProtKB:P02787) GO:0060586 - multicellular organismal iron ion homeostasis IEP WB occurs_in(UBERON:0002114) duodenum
human TFRC (UniProtKB:P02786) GO:0060586 - multicellular organismal iron ion homeostasis IEP WB occurs_in(UBERON:0002114) duodenum
Cellular Component
Tf, transferrin cell tip GO:0051286 IDA RGD Figure 5 - ID, 15 min; text description
Tfrc, transferrin receptor cell surface GO:0009986 IDA RGD Figure 5; text description
Tfrc, transferrin receptor GO:0031528 - microvillus membrane IDA WB
Tf, transferrin, Fth1, Ftl1, ferritin GO:0005615 - extracellular space IDA WB
Molecular Function
Fth1, Ftl1, ferritin iron ion binding, GO:0005506 IDA FB, Tair, WB occurs_in UBERON:0000320 duodenal mucosa Which ferritin subunit?
Tf, transferrin iron ion binding, GO:0005506 IDA FB, Tair, WB occurs_in UBERON:0000320 duodenal mucosa
Tf, transferrin ferric iron binding GO:0008199 IDA RGD, SGD
ferritin ferric iron binding GO:0008199 IDA SGD
Tfrc, transferrin receptor GO:0004998 - transferrin receptor activity IEP WB occurs_in(UBERON:0008346) duodenal epithelium IEP for MF annotation???

Minutes

  • On call: Alice, Barbara, Edith, Giulia, Helen, Kimberly, Li, Midori, Olivia, Paola, Paul T., Penelope, Petra, Sabrina, Sage, Stacia, Stan, Tanya, Val

Next GOC Meeting - USC, Los Angeles, CA, November 4-6, 2016

  • Please register if you haven't already
  • Please check the meeting agenda to see what topics will be discussed
    • If you are interested in raising a topic for discussion, please add it along with your name and the amount of time you think will be needed

Annotation Consistency Exercise

  • Issues we discussed:
    • Determining what annotations could be made to ferritin
      • Authors used an antibody, but didn't say exactly what the antibody recognized and there are many different potential subunits to the rat ferritin complex (light and heavy chains)
    • Differences in evidence code usage
      • Most curators used IDA for the transport annotations, but there was also IEP
      • There was some discussion about use of IC to support annotations, as there didn't seem to be a single experiment that showed both iron binding and transport
    • Support for iron homeostasis annotations?
      • We discussed whether an iron homeostasis annotation added much if the proteins were already annotated to irton transport
      • Did the experiments simply show support for nutrient uptake or was there also support for homeostasis?
    • Annotations to intestinal absorption
      • Seems a broad, high level term to use, but could be made more specific with annotation extensions, e.g. has_input(ferric ion), or by requesting a new, more granular term like intestinal iron absoption.
      • For terms like intestinal iron absorption, the potential list of terms could get very long - is this necessary? Would an alternative term such as intestinal metal ion absorption be a reasonable alternative?
    • Additional papers with knock-down experiments might help to better support the Biological Process annotations
    • Cellular component annotations
      • What evidence is sufficient to annotate to cell surface vs a membrane term? Note that this issue has been raised before and will be discussed at the GOC meeting next month.
    • Molecular function annotations
      • What evidence would support the transferrin receptor activity annotation? Maybe IC, but not IEP.
  • Review of Noctua model:
    • Ferritin is represented in this model by the generic GO complex, so no specific annotations to a rat complex, or particular subunits, would be made
    • The model represents the relation between transferrin and the transferrin receptor as 'directly provides input for'
      • David was not certain that this was the best relation to use, but wanted to capture the idea that there was some sort of causal relation between the transferrin and the transferrin receptor that led to uptake into the epithelium
    • Note that it would be fine to use evidence from more than one paper to support a given LEGO model

Discussion of Outstanding github Tickets