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Category:RefGenome Electronic Jamboree 2009-07 SLC11A1/2

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See the talk page for discussion. See also Help:Annotation Jamborees

Orthoset

Ortholog set at PPOD

Participants

Name Group Organism(s)/Genome(s) Notes

Rob Nash

SGD

S. cerevisiae

Stan Laulederkind

RGD

Rat

Petra Fey

dictyBase

D. discoideum

Pascale Gaudet

dictyBase

D. discoideum

Li Ni

MGI

Mouse

Slc11a1=MGI:1345275=UniProtKB:P41251 Slc11a2=MGI:1345279=UniProtKB:P49282

Dmitry Sitnikov

MGI

Mouse

Slc11a1=MGI:1345275=UniProtKB:P41251

Susan Tweedie

flyBase

D. melanogaster

Brenley McIntosh

ecoliwiki

E. coli

ECOLI:mntH (P0A769)

Jodi Hirschman

SGD

S. cerevisiae

Emily Dimmer

GOA

Human

Yasmin Alam-Faruque

GOA

Human

Rachael Huntley

GOA

Human

Varsha Khodiyar

BHF-UCL

Human

Ruth Lovering

BHF-UCL

Human

Debby Siegele

ecoliwiki

E. coli

ECOLI:mntH (P0A769)

Kimberly Van Auken

WormBase

C. elegans

smf-1=WBGene00004876, smf-2=WBGene00004877, smf-3=WBGene00004878

Ranjana Kishore

WormBase

C. elegans

smf-1=WBGene00004876, smf-2=WBGene00004877, smf-3=WBGene00004878

Lakshmi Pillai

AgBase

G. gallus

Tanya Berardini

TAIR

A. thaliana


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Annotations

no genes found in this category

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Notes

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  • When a fusion to a reporter protein, such as GFP or PhoA, is used to determine the localization of a membrane protein, is it appropriate to use the IDA evidence code? Based on a search of the Gene Ontology website, that seems to be what dictyBASE and SGD have done in the past. Is that still the case? Debby (WB also annotates membrane protein::GFP fusions to CC terms using the IDA evidence code. --Kimberly)
  • Does functional expression inform subcellular localization? For example, if a transporter is expressed in Xenopus oocytes and experiments demonstrate functional transporter activity, can a Cellular Component annotation be made? If so, with what evidence code? --Kimberly

For just the mammalian A1 genes see Category:SLC11A1


Minutes

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SLC11A1/2 Jamboree Notes

  • Summary of Action Items (also embedded in context of discussion below)

ACTION ITEM: Debby could send a link to where E. coli group was looking in the documentation regarding IDA vs IMP for subcellular localization of fusion proteins

ACTION ITEM: (from ruth) next jamboree, decide on proteins, try to encourage ontology experts for relevant branches of the ontology to participate

ACTION ITEM: add equivalent metal ion terms to the ontology for different metal ions

ACTION ITEM: there's a link to the binding term documentation on the talk page - please give feedback to work out a range of opinions before the consortium meeting

ACTION ITEM create a wiki page where people can start suggesting/annotating genes for future jamborees to encourage broader participation


  • Items from talk page:

Jim and Brenley - can you use IDA or IMP if you are measuring the localization of a GFP-fusion protein?

Emily - GOA uses IDA if localization is intended to be a measure of the wild-type protein Don't really use IMP for localization annotations. IDA or not at all.

Pascal - Only time to use IMP would be for comparing WT vs mutant protein.

Debby - seems reasonable What is in the evidence code documentation? SGD and dicty both use IDA.

Could improve the documentation.

ACTION ITEM: Debby could send a link to where E. coli group was looking in the documentation.


  • Related component question:

Does a functional assay inform localization?

GOA would annotate to a component term using IDA.

MGI, WormBase, coli would use IC in these cases, as there is no direct localization data.

Isn't the functional assay enough?

Jim: isn't this analogous to a TF localizing to the nucleus? This is the example on the GO evidence code documentation page.

How do these two situations differ? What actually happens in transfection experiments when a reporter and a TF are transfected together?

Could we leave this issue up to the individual curator?

Wasn't the point of IC to illustrate that there was no direct evidence? Isn't IC a safer annotation?

Two experiments: measure transporter activity AND immunolocalization test to show membrane location Would this be better?

Is expression in an oocyte reflective of normal localization? This is a general concern for expressing a protein outside of its normal environment.

Pascal: problem with IC -- there are two kinds: those based on ISS, those based on a direct assay a cc annotation in this case would be more like one based on a direct assay

Ruth: if these people have actually done an immunofluorescence assay, would we be happy with an IDA if you're showing its functional, it's like doing an immunofluoresence assay

Li: we agree that we don't transfer IC from ISS? if there is experimental evidence, we can use IC

the documentation, however, allows IC from ISS or even IEA

Susan: try to find experimental evidence first would favor annotation to species being annotated, though


  • Annotating to transport process terms from transporter activity assays

Emily - found a number of papers measured the capacity of this gene product to transport a number of different cations transported, but only a few of these have evidence for a proper physiological basis iron, manganese, possibly lead or copper, but authors also cite experiments for cadmium, cobalt, nickel, etc. across membranes

some of the cations don't seem to have any obvious usefulness in the human body we were quite unsure of how to annoate these experiments. came across a paper where the research community seemed unsure of which transport functions are relevant could there be a role in detox of metal ions?

it's interesting that it has this activity, it'd be useful to see the full range of activities

GOA has annotated individually for each of the different transport activities and also included some NOT annotations

the question: what biological process annotations? for only a few annotations is there physiological relevance known?

could annotate to ion transport, but do we want to provide transport processes for each of the ions transported e.g. cobalt ion transport. link MF and BP annotations? how far to go? investigators aren't sure themselves, assay all sorts of cations for this protein this is a normal wild-type protein just being assayed for different types of transport

Pascal: in terms of tranpsort, the mf and bp terms are essentially synonymous

Tanya: make the process annotations as well as the MF annotations

Emily: normally it would never come into contact with these ions, e.g. vanadium

vanadium is used in some drugs

E: investigators acknowledge a grey area for what is physiologically relevant

Tanya: down the road, someone might be experimenting with these ions and looking for transport(er) terms

P: the function and the process are essentially synonymous is there a situation where you would not make the transport annotation for the transporter activity?

No.

Debby: another example--one of the recent ref genome targets there were e. coli enzymes that were shown to hydrolyze a whole bunch of sugar substrates, all have a broad range of overlapping activities, but it's not clear what biological process those activities are associated with. debby felt comfortable annotating showing the activity, but was hesitant to say it was involved in the substrate metabolism without additional evidence.

Jodi: typically would not make an annotation to process, for in vitro assay, would just leave the function annotation

debby: should we annotate to the biological transport process?

pascal: also depends upon the genomic context - if you have a single enzyme, it's probably the one involved in the process

susan: annotate according to the intent of the authors - annotate to metal ion transport, but not each individual transport term.

ruth: affinities could inform the annotations - what are relevant levels of solutes? agree with susan, if the authors were quite hesitant, unless curators feel confident authors are dealing with physiological levels of ions, then make the annotation.

debby: there's a difference between going with what the authors intend vs going past what the authors intend

tanya: but then why do they present the data? we're annotating to the experiments.

pascal: authors don't really know the significance

emily: it does seem the affinity for transport doesn't necessarily correlate with in vivo activity

pascal: an annotation to lead transporter activity, why not to lead transport?

ruth: several papers and reviews have been published, numerous groups are not willing to say that these proteins are involved in a given metal ion transport process

tanya: the structure of the ontology is such that metal ion transport will be found if annotations are made to the more specific child term

what ions are physiologically relevant?

why would the terms be in the ontology if they weren't biologically informative?

pascal: humans have evolved ways to deal with all kinds of toxic chemicals

debby: reading the introduction of the paper that emily put the pubmed id up for--this protein is a widely expressed ferrous iron transport that plays a vital role in iron homeostasis, general agreement for role in iron transport biochemically common to check other ions to characterize the transporter, but how specific are the transporter activites? would feel very confident annotating to metal ion transport and maybe based on other papers annotate to more specific biological process terms. wouldn't feel comfortable annotating to more specific terms from this paper, unless there was some other evidence that is was involved in that biological process. mf annotations would help people get to these gps.

discussion of transport terms

ruth: think about the intent of the authors. in this case, the authors don't intend to prove that cadmium is transported by this protein. because there are so many different metal ion transporters, you can't be sure which ones actually tranport in vivo

tanya: the potential is what can be annotated

ruth: the authors do not intend to show that this is the enzyme that actually does this process. could do this experiment with a variety of different transporters, but that isn't the experiment they did.

pascal: how would you be convinced, in human, to annotate to iron transport?

ruth: if there was a mutation in humans that affected iron levels, that would be very good evidence.

pascal: but these are very large gene families

ruth: but the authors don't intend to prove that this particular transporter is involved in this process


  • Homeostasis term annotations

emily: when to annotate to homeostasis terms? this protein transports ions and knock-outs are associated with anemia? do people co-annotate to iron homeostasis? homeostasis is the regulation of the process of ion transport? can't get homeostasis if the transporter is knocked out how much information is needed for an IMP annotation to iron homeostasis?

would anyone have a problem with iron homeostasis?

No, sounds reasonable.

should iron transport be related to iron homeostasis? should transport be a part_of homeostasis?

would you have a term, vanadium homeostasis?

how do people feel about a formal part_of link between transport and homeostasis?

if you're moving ion levels around, aren't you also affecting the homeostatic process? is this a leap too far? maybe just put a comment in for the transport term

would probably want to annotate to homeostasis if you were convinced that ion actually had a role in your organism maybe that's a reason for putting this into the comments for the term

petra: would now annotate to homeostasis terms for the dicty protein

jim: iron homeostasis seems to be a very central role for the transporters would you make a homeostasis annotation for a calcium transporter?

ruth: return of levels of calcium to resting state could be annotated to homeostasis

pascal: was anyone involved in the reorganization of the transport branches of the ontologies?

tanya: there was a transport group...who was in it?

pascal: have transport annotation guidelines? some very basic things we're talking about, but we don't all seem to be annotating the same way

ACTION ITEM: (from ruth) next jamboree, decide on proteins, try to encourage recent ontology experts to participate


  • Ontology development for metal ion terms

emily: creating different annotations for different metal ions because there's a lack of terms to describe different metal ions equivalent terms for iron and manganese don't exist

ACTION ITEM: add equivalent metal ion terms to the ontology for different metal ions


  • Binding term documentation
  • ruth: binding terms

had a binding term annotation conference call ruth has written out the minutes and proposed guidelines please take a look

from the meeting, we were not going to do any ICs for binding?

the concepts discussed in the binding meeting--if a protein has iron transport activity, you don't have to annotate to iron binding if there's a direct experiment to test for iron binding, then add the annotation otherwise, just annotate to the transport activity

debby: thought the conclusion was that you didn't need to do it, but that it was okay to do it

ruth: it'd be really great to finish off this documentation. if this is still not clear, then the binding discussion group needs to sort this out.

it'd be good to resolve this and get the proposal agreed upon at the September consortium meeting.

ACTION ITEM: there's a link to the binding term documentation on the talk page - please give feedback to work out a range of opinions before the consortium meeting


  • Suggestions for jamboree genes to encourage broader participation

emily: a really good idea from Li regarding selection of targets

have a table of a number of potential targets, each group could indicate the number of papers to help get maximal participation in the calls

mgi/goa are often overwhelmed by the number of papers, other groups have very little literature

ACTION ITEM:pascal: start making the page now and people can start suggesting/annotating the genes

References

See Help:References for how to manage references in GONUTS.

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