Difference between revisions of "LEGO Curation"

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Revision as of 14:10, 6 February 2017

Agenda

Logins

LEGO Principles

  • Pieces of biological information are connected using a controlled vocabulary of relations
  • Assertions made using these relations are supported with evidence statements, i.e. ECO codes, references
    • Evidence from more than one paper may be used within a single model
    • Evidence from more than one paper may be used to support a single assertion
  • LEGO models are 'models of instances' meaning that these are models of specific individuals and events

LEGO at its Most Basic

  • Molecular functions are enabled_by genes/gene products
  • Molecular functions may be part_of larger biological processes
  • Molecular functions occur_in some location
    • Subcellular locations are part_of some larger anatomical structure

LEGO Beyond Basics

  • Some biological processes and molecular functions regulate other biological processes
    • The regulation may be positive or negative and may be 'direct' or 'indirect'
  • Some biological processes and molecular functions are causally upstream of other biological processes
  • Sometimes you don't know how two things are related - 'causally upstream of or within'

Paper for Curation

  • The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis in Caenorhabditis elegans. PMID:27881675
  • The entities:
    • cua-1 (WBGene00000834)
      • WP:CE26305 CUA-1, isoform a, 1238 aa
      • WP:CE19271 CUA-1, isoform b, 1116 aa
    • cuc-1 (WBGene00000835)
    • pgp-2 (WBGene00003996)
  • 2 uM is optimal Cu for C. elegans growth
  • Summary figures at the end of papers, e.g. Figure 7B in this paper, or in reviews can be very helpful for LEGO models, but assertions need to be supported by as much evidence as possible
  • What is the role of CUA-1 when Cu levels are optimal? When Cu levels are toxic? When Cu levels are limiting or zero?
  • Link to collaborative model

CUA-1 Molecular Function

  • Is the molecular function demonstrated in this paper?

pg. 4 To further confirm whether the CUA-1.1::GFP translational fusion protein can transport Cu, we exploited previously established assays in Atp7a+/+ and Atp7a-/- mouse embryonic fibroblasts (MEFs) (24). Atp7a-/- MEFs transiently transfected with CUA-1.1::GFP showed increased expression of Cu chaperone for superoxide dismutase (CCS), indicating decreased levels of cellular Cu (25,26) as compared to Atp7a-/- MEFs transfected with an empty vector (Supplemental Fig. S3A). Over-accumulated Cu in Atp7a-/- MEFs was rescued by ectopic expression of CUA-1.1::GFP (Supplemental Fig.S3B), further indicating that CUA-1.1 can export Cu. Moreover, these results demonstrate that a C-terminal GFP tag does not significantly interfere with CUA-1 function.

 is_a GO:0005375 copper ion transmembrane transporter activity
   part_of GO:0060003 copper ion export
   is_a GO:0043682 copper-transporting ATPase activity
     GO:0004008 copper-exporting ATPase activity
  • What is the correct evidence code?

What are the Biological Processes?

Copper-Related Terms

  • GO:006003 copper ion export
    • Contextual information to indicate start location and end location?
  • GO:0055070 copper ion homeostasis
  • GO:0006878 cellular copper ion homeostasis
    • GO:0097580 intracellular sequestering of copper ion
      • part_of cellular copper ion homeostasis
      • No annotations - any organism
      • Note that this is a child of localization but not transport
  • GO:1990169 stress response to copper ion

Development-Related Terms

  • GO:0002119 nematode larval development
  • GO:0009792 embryo development ending in birth or egg hatching
  • GO:0048609 multicellular organismal reproductive process
    • GO:0090728 negative regulation of brood size
  • GO:0040010 positive regulation of growth rate

Other Processes

  • transcription from RNA polymerase II promoter
  • gut granule assembly

Where do the Molecular Functions Occur?

Expression Patterns

  • Subcellular locations
    • Basolateral plasma membrane
    • Plasma membrane
    • Golgi membrane
    • Gut granule
  • Tissue locations
    • Intestine
    • Hypodermis
    • Neurons
    • Pharynx

Site-of-Action Studies

  • Tissue-specific RNAi
    • Intestine
    • Muscle
    • Hypodermis
  • Tissue-specific expression
    • Intestine

CUA-1.1 Expression

Tissue Expression Sub-tissue Expression Subcellular Localization Life stage Tissue-specific Knockdown (Embryonic Lethal Phenotype) Tissue-specific Rescue (Embryonic Lethal Phenotype) Tissue-specific Knockdown (Reduced Fecundity/Low Brood Size) Tissue-specific Rescue (Reduced Fecundity/Low Brood Size) Tissue-specific Knockdown (Growth) Tissue-specific Rescue (Growth)
Intestine Anterior intestine, mainly concentrated Basolateral membranes, intracellular compartments Intestine Intestine (under control of vha-6 promoter) Reduced fecundity
Hypodermis Sever reduction in brood size under low dietary copper
Neurons
Pharynx -

What are the other players and how do we define their roles?

  • cuc-1 (WBGene00000835)
  • pgp-2 (WBGene00003996)
  • copper - see ChEBI entries