Noctua

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Summary

Noctua is an online system for making extensible GO annotations, which we call "GO-CAM models". Anything from simple annotations to complicated pathways are supported. However, the overall goal should be for a model to represent a unit that roughly corresponds to a biological pathway. This document describes how to make GO-CAM models using Noctua. File:Background slides on family and function evolution.pdf

Requirements

A web browser. Chrome is recommended.

Launching Noctua

Setup

  • Before using Noctua to edit or create models, please follow this procedure to request edit access. You will need a ORCID (https://orcid.org), so you can be uniquely identified. Each part of a Noctua model is individually attributed to an editor, as well as the project that provided their funding (if applicable).

Using Noctua

Login

You can view models without logging in, but you must log in before creating new annotations (by editing an existing model, or creating a new model). Click on the Login button in the right upper corner of the page. There are several options for logging in. We recommend using Github (if you don't already have an account just go to http://github.com).

Editing an existing model

Just click on the "Edit" button in the rightmost column of the model list. The model list can be filtered using the search box just above the list of available models.

Starting a new model

Just click on the blue "Create Noctua Model" button.

What is a Noctua model?

Molecular activity

Each Noctua model consists of at least one MOLECULAR ACTIVITY (FUNCTION), carried out by at least one GENE PRODUCT. Ideally, all of the following “aspects” of the gene product’s function will be specified in the model. However, in cases where some or most of these aspects are unknown, a model may still be constructed with details added as more information becomes available. Users should attempt to specify functions as fully as possible, but partial models are expected and still contribute to the GO knowledgebase. The following aspects are represented in a model:

  • Molecular function (MF): the molecular activity carried out by a gene product as part of a larger biological process; this is specified by a term from the GO molecular function ontology. MF may be qualified, using defined relations, as follows:
    • If the function acts upon another “target” molecule, this can be specified using a gene product identifier (for a protein or a gene) or term from the ChEBI ontology (for a small molecule)
    • If the function acts during a particular “biological phase” (e.g. a particular stage in organism development), this can be specified using a term from an appropriate ontology
  • Cellular component (CC): the location of the gene product when it is carrying out its activity; this is specified by a term from the GO cellular component ontology. CC may be qualified, using defined relations, as follows:
    • If the activity occurs in a specific cell type, this can be specified using a term from a Cell Type or Anatomy Ontology.
    • If the activity occurs in a specific anatomical structure, this can be specified using a term from the Uberon, or other organismal Anatomy, ontology.
  • Biological process (BP): the larger “biological program” to which the activity contributes; this is specified by a term from the GO biological process ontology. BP may be qualified, using defined relations, as follows:
    • If the process is a part of a larger biological program, it can be linked to the larger biological program with another GO biological process term.

All of these aspects together constitute a unit of annotation, which we call an “annoton”. Each annoton is centered on the molecular activity, as this is the most basic description of gene product function.

Molecular activities can be linked by causal relations

Activities can be linked together by relations that describe their causal dependence. The most common relations are “regulates” and “provides input for”, but there are other relations of greater and lesser specificity, depending on what is known. “Regulates” should be used to denote biological control of a downstream activity. “Provides input for” should be used when there is no control, but an upstream function creates a molecular entity that is the target of the downstream function, such as in a metabolic pathway.


Creating a new activity and its properties

First, create each molecular activity using the “Simple annoton editor” tool, available in the Workbench menu: Workbench -> Simple annoton editor

Fig. 1 Launching the simple annoton editor

This will launch a new browser tab

Step 1. Fill in the form

Fill in as many fields as possible in the form, by typing in the field, and then selecting from the autocomplete suggestions by moving the mouse over your selection and clicking. Tips:

  • The required fields are gene product, molecular function and evidence for the function. All other fields are optional.
  • You can annotate a complex instead of a single gene product, by choosing "macromolecular complex" from the drop-down menu
  • For gene products, you can type in the gene symbol, e.g. Wnt3a. If necessary to narrow down the choices, type a space after the symbol, and enter the three letter code for the species (first letter from genus and two from species name, e.g. mmu for Mus musculus). Each entry in the autocomplete will also show the associated unique database identifier or accession, so curators can confirm that they are selecting the appropriate entity for annotation.
  • In general, enter a space after a complete word, to narrow down the choices.

Just as in conventional GO annotation, you must fill in the Evidence and Reference fields for each line of annotation, or an annoton will not be created. We recommend that you fill in as many fields as possible before creating the annoton, as after it is created, you will need to edit it from the graph canvas, which requires more steps to do. Press the “Create” button. A new annoton will appear on the graph canvas (the main window). Tips:

  • Each new activity will appear on the same part of the canvas, so if you add more than one annoton you will need to move them around on the canvas (by clicking and dragging) to see the ones underneath.

After either selecting an existing model or starting a new one, you will see the graph view by default. To create a new annoton, The analogy is to a library. You will first find and check out (lock) the families you want to curate, and then select a family to curate from your list of locked families. All families now have a curation status (curated, partially curated, uncurated).