Annotation Conf. Call 2016-06-28

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Bluejeans URL

https://bluejeans.com/993661940

Agenda

Annotation Consistency Exercise

Abstract The mechanisms that constrain memory formation are of special interest because they provide insights into the brain's memory management systems and potential avenues for correcting cognitive disorders. RNAi knockdown in the Drosophila mushroom body neurons (MBn) of a newly discovered memory suppressor gene, Solute Carrier DmSLC22A, a member of the organic cation transporter family, enhances olfactory memory expression, while overexpression inhibits it. The protein localizes to the dendrites of the MBn, surrounding the presynaptic terminals of cholinergic afferent fibers from projection neurons (Pn). Cell-based expression assays show that this plasma membrane protein transports cholinergic compounds with the highest affinity among several in vitro substrates. Feeding flies choline or inhibiting acetylcholinesterase in Pn enhances memory, an effect blocked by overexpression of the transporter in the MBn. The data argue that DmSLC22A is a memory suppressor protein that limits memory formation by helping to terminate cholinergic neurotransmission at the Pn:MBn synapse.

  • How to capture biological process aspects of memory?
    • The paper identifies a ‘memory suppressor gene’ (Solute Carrier 22A of Drosophila (DmSLC22A) (FlyBase:CG7442; FBgn0037140). How to capture the biology described - memory, learning, conditioning? What new terms are needed to capture the process? Alternatively, is it better to capture these experiments only as phenotypes?
    • Leave the expression/mechanistic sections and have a look at these four sections of this paper:
      • Drosophila CG7442 Is a Memory Suppressor Gene Functioning in MBn and DAn
      • Drosophila CG7442 Overexpression Impairs Memory
      • DmSLC22A Regulates Both Memory Acquisition and Retention
      • DmSLC22A Modulates Memory Strength by Regulating Cholinergic Neurotransmission in the MB Calyx

Annotations

Gene/Marker Name GO term Evidence Code With/From Annotation Extension Comment
Biological Process
SLC22A NT:negative regulation of olfactory memory retention (not forgetting)?
SLC22A NT:positive regulation of memory acquisition (learning?)
SLC22A NT:negative regulation of memory retention (memory)
SLC22A NT:negative regulation of memory IMP
SLC22A NT:regulation of memory acquisition IMP
SLC22A NT:regulation of memory retention IMP
SLC22A NT:negative regulation of memory IMP
SLC22A NT:negative regulation of anesthesia-resistant memory IMP
SLC22A regulation of olfactory learning (GO:0090328) IMP
SLC22A NT:positive regulation of rate of learning IMP
AChE NT:negative regulation of memory IMP
SLC22A NT:negative regulation of memory IGI AChE
AChE NT:negative regulation of memory IGI SLC22A
SLC22A negative regulation of synaptic transmission, cholinergic (GO:0032223) IMP
SLC22A NT:neurotransmitter transport involved in regulation of memory IC GO:0015220|GO:NT: negative regulation of memory
SLC22A NT:cholinergic synaptic transmission involved in regulation of memory This one's a "maybe"
SLC22A NT:negative regulation of memory IMP/IDA part_of (olfactory learning)
SLC22A NT:negative regulation of olfactory learning IMP/IDA
SLC22A memory (GO:0007613) IMP occurs_in(DAn),happens_during(adult life stage)
SLC22A NT: negative regulation of acetylcholine receptor signaling pathway via acetylcholine uptake involved in memory acquisition rate enhancement? occurs_in(DAn),happens_during(adult life stage)
SLC22A NT: negative regulation of acetylcholine receptor signaling pathway via acetylcholine uptake involved in memory retention suppression? occurs_in(DAn),happens_during(adult life stage)
AChE memory (GO:0007613) IMP How to express an extracellular synaptic region between two different neurons via annotation extensions?
AChE NT: negative regulation of acetylcholine receptor signaling pathway via acetylcholine catabolism involved in memory acquisition rate enhancement?
AChE NT: negative regulation of acetylcholine receptor signaling pathway via acetylcholine catabolism involved in memory retention suppression?
SLC22A NT:negative regulation of olfactory memory IMP acts_on_population_of mushroom body neuron; dopamine neuron olfactory memory,pos. reg., children of olfactory learning (GO:0008355). From Fig1,2 (MbN and DpN need to be component terms).
SLC22A NT:positive regulation of olfactory learning IMP child of olfactory learning (GO:0008355). From fig 5c. Rate of learning is impaired in knockdown.
SLC22A regulation of synaptic transmission, cholinergic (GO:0032222) IMP
SLC22A NT: choline uptake? IDA
SLC22A dopamine uptake (GO:0015872) IDA
SLC22A histamine uptake (GO:0051615) IDA
SLC22A NT: amino-acid betaine uptake? IDA
Molecular Function
SLC22A amino-acid betaine transmembrane transporter activity (GO:0015199) IDA
SLC22A acetylcholine transmembrane transporter activity (GO:0005277) IDA
SLC22A choline transmembrane transporter activity (GO:0015220) IDA
SLC22A dopamine transmembrane transporter activity (GO:0005329) IDA
SLC22A NT: histamine transmembrane transporter activity IDA
SLC22A acetylcholine transmembrane transporter activity (GO:0005277) IDA/IMP
SLC22A choline transmembrane transporter activity IDA
SLC22A acetylcholine transmembrane transporter activity IDA
SLC22A choline transmembrane transporter activity (GO:0015220) IDA
SLC22A acetylcholine transmembrane transporter activity (GO:0005277) IDA
Cellular Component
SLC22A dendrite (GO:0030425) IDA part_of (calyx of adult mushroom body)
SLC22A plasma membrane (GO:0005886) IDA
SLC22A dendrite (GO:0030425) IDA part_of(cholinergic neuron), part_of (calyx of adult mushroom body)
SLC22A dendrite (GO:0030425) IDA part_of(a/b MBn),part_of(a'/b' MBn)
SLC22A NT:dendrite plasma membrane IC GO:0030425,GO:0005277,GO:0051630 part_of(a/b MBn),part_of(a'/b' MBn) Would need to use GO_REF:0000036
  • Other comments: "Not clear what the differences between memory retention and learning."

I really don't understand the stuff about interference and forgetting. Overall I'm not fully convinced the set of memory BP annotations is self-consistent and sensible. Annotations like increased/decreased olfactory memory for RNAi and overexpressors should be phenotype annotation

Protein Binding Annotations

 The 'with' column (8) and the annotation extension column (16) should be used only for direct interactions and only when the binding 
 relationship is not already included in the GO term and/or definition. See "column 16 documentation for relationship types to use when 
 adding IDs in the annotation extension column (16). 
  • Some groups do annotate protein binding from experiments that do not assess direct physical interactions, such as co-IP.
  • Proposal has been made to update documentation to be clearer about how the GOC members annotate protein binding.
  • Any objections to updating the documentation? Suggestions for clearer wording?

Minutes

  • On call: Alice, Bob, David OS, Edith, Elena, Giulia, Helen, Kimberly, Li, Melanie, Midori, Paola, Petra, Rebecca, Sabrina, Shur-Jen, Stacia, Stan, Tanya

Annotation Consistency Exercise

  • Molecular Function and Cellular Component annotations were all generally the same; no problems there
  • Biological Process annotations generated more discussion
    • Consensus seemed to be that this is an area of the ontology that would benefit from further development, with input from experts in the learning and memory field
      • There is a NeuroBehavior Ontology - who uses that ontology and would it be helpful for GO to work with that?
    • Paper raises the issue of what specific aspects of memory we want to capture in GO
      • Memory acquisition?
      • Memory retention?
      • Memory interference?
    • We also want to make sure we understand how the results of assays used to assess different aspects of learning and memory inform BP term choice
    • Tentative plan: compare learning and memory papers across organisms to find commonalities that could be used to develop GO BP
    • Useful review:What is memory? The present state of the engram

Protein Binding Documentation

  • Review of different group's practices for capturing protein binding annotations indicates that there are still some differences with respect to what interactions groups capture
  • Some groups are more inclusive than others based largely on methodology and interpretation of author intent
  • Another contributing factor is whether or not groups have another mechanism in place, e.g. BioGrid or IntAct, to capture these physical interactions. Would be good to follow-up with IntAct to confirm what interactions they export to GOC and why.

===== I asked Sandra for more details and she said:

From http://www.ebi.ac.uk/intact/about/faq?conversationContext=5#8

How are binary interactions selected for export to UniProtKB/GOA records? All binary interactions evidences in the IntAct database, including those generated by Spoke expansion of co-complex data, are clustered to produce a non- redundant set of protein pairs. Each binary pair is then scored, using a simple addition of the cumulated value of a weighted score for the interaction detection method and the interaction type for each interaction evidence associated with that binary pair. Only experimental data is scored, inferred interactions, for example, would not be scored, and any low confidence data, or data manually tagged by a curator for exclusion from the process, are also not scored. Isoforms and post-processed protein chains are regarded as individual proteins for scoring purposes. Score weightings were determined using the PSI-MI CV

Once the interactions have been scored, a cut-off filter of 9 has been established, below which the interaction is not exported to UniProtKB and to the Gene Ontology annotation files. Additional rules ensure that any protein pair scoring above 9 must also include at least one evidence of a binary pair, excluding spoke expanded data, before export to UniProtKB/GOA.

These criteria ensure that

   * Only experimental data is used for making the decision to export the protein pair to UniProtKB/GOA as a true binary interacting pair
   * The export decision is always based on at least two pieces of experimental data. A single evidence cannot score highly enough to trigger an export
   *  An export cannot be triggered if the protein pair only ever co-occurs in larger complexes, there must be at least one evidence that the proteins are probably in physical contact.

IMEx will only call an interaction 'direct' when performed with 2 purified molecules in vitro so any method using whole cells or cell lysates would not be regarded as direct. The described methodology will give you binary i.e. either direct or involved in the same small complex. =====

  • Consensus was, though, that this is an area of annotation where it is okay to have some differences but the documentation should reflect this
  • ACTION ITEM: Draft new statement explaining diverse GOC approach to protein binding annotations. Review at a future call to make sure everyone is okay with it.