Help: Key Events

A-D Create a New Key Event


KE ID

When a KE is created, an ID number is automatically assigned to it. This number is used for tracking the KE in the AOP-KB.

Title

The KE title should describe a discrete biological change that can be measured. It should generally define the biological object or process being measured and whether it is increased, decreased, or otherwise definably altered relative to a control state. For example “enzyme activity, decreased”, “hormone concentration, increased”, or “growth rate, decreased”, where the specific enzyme or hormone being measured is defined.

On the ‘Key Events’ page, https://aopwiki.org/events, upon selecting the “New key event” button, the user will see a ‘New Key Event’ form with fields for the entry of a ‘Title,’ ‘Short name,’ and a drop down menu for selection of a level of Biological Organization. Upon filling out these fields, click ‘Create key event’ to create a new key event. Upon creation, user will be directed to a new page for this event.

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. The short name should be less than 80 characters in length.

Level of Biological Organization

Structured terms, selected from a drop-down menu, are used to identify the level of biological organisation for each KE. Note, KEs should be defined within a particular level of biological organisation.

To edit the “Level of Biological Organization” section, on a KE page in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Key Event” listing the Event title and short name, with a drop down for Biological organization. Click on the arrow and select a biological organization from Molecular to Population level. On the upper right hand menu, click ‘Update event’ to add the biological organization and return to the Key Event page.  The biological organization should appear under the “Biological Context” heading on the KE page.

E Event Components and Biological Context


Cell Term/Organ Term

Further information on Event Components and Biological Context may be viewed on the attached pdf.

The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.

To add a Cell Term or Organ Term, on the KE page, in the upper right hand panel menu, click 'Edit.' This brings you to a page entitled, "Editing Key Event." In the "Cell term" field, type the term you wish to add, and a list of options will appear in the drop down menu below. Select the term that you wish to add, and click 'Update' in the upper right hand menu. You will be returned to the Key Event page with the new term appearing under the "Cell term" field. Follow the instructions similarly to add an Organ term.

To remove a Cell Term, on the KE page, in the upper right hand panel menu, click 'Edit.' This brings you to a page entitled, "Editing Key Event." In the "Cell term" field, delete the existing text, and click 'Update' in the upper right hand menu. You will be returned to the Key Event page and the term should no longer be present in the "Cell term" field. Follow the instructions similarly to remove an Organ term.

Event Components

Further information on Event Components and Biological Context may be viewed on the attached pdf.

Individual KEs have one or more “event components” consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies. Biological process describes dynamics of the underlying biological system (e.g. receptor signaling). The biological object is the subject of the perturbation (e.g. specific biological receptor that is activated or inhibited). Action represents the perturbation of this system described by the other two terms that results in this key event (e.g. ‘decreased’ in the case the a receptor is inhibited to indicate a decrease in the signaling by that receptor). 

On a KE page, next to the heading “Key Event Components,” click ‘Add event component’ to go to a new page entitled “New Event Component.” This page lists the associated Event Component and has fields for Process, Object, and Action.  These fields can be searched for existing Biological Process, Object, and Action terms associated with the level of organization of the KE.  For example, an existing Biological Process for a KE at the cellular level could be “translation.” For more specific terms, continue typing until the term you desire appears in the drop down list of choices. Filling in one or more of these fields and then clicking ‘Event Component suggestions’ will bring up a drop down menu listing existing Event Components. Clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests.

Clicking ‘Add event component’ will return the user to the KE page where the new event component will be listed in the Key Event Components table. Multiple Event Components may be added.

To remove an event component, click 'Remove' next to the component you wish to remove. You will be returned to the KE page with the record removed from the Key Event Components table.

Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.

F AOP Information


AOPs Including this Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. Clicking on the name of the AOP will bring you to the individual page for that AOP.

G-H Describe the Key Event


Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. For example, the biological state being measured could be the activity of an enzyme, the expression of a gene or abundance of an mRNA transcript, the concentration of a hormone or protein, neuronal activity, heart rate, etc. The biological compartment may be a particular cell type, tissue, organ, fluid (e.g., plasma, cerebrospinal fluid), etc. The role in the biology could describe the reaction that an enzyme catalyses and the role of that reaction within a given metabolic pathway; the protein that a gene or mRNA transcript codes for and the function of that protein; the function of a hormone in a given target tissue, physiological function of an organ, etc.

To edit the “Key Event Description” section, on a KE page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Key Event.” Scroll down to the “Key Event Description”  section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update event’ to save your changes and return to the KE page or "Update and continue" to continue editing text sections.  The new text should appear under the “Key Event Description” section on the KE page.

How it is Measured or Detected

One of the primary considerations in evaluating AOPs is the confidence and precision with which the KEs can be measured. The aim of this section of the KE description is not to provide detailed protocols, but rather to capture, in a sentence or two, per method, the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements. Methods that can be used to detect or measure the biological state represented in the KE should be briefly described and/or cited.

To edit the “How It Is Measured or Detected” section, on a KE page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Key Event.” Scroll down to the “How It Is Measured or Detected” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update event’ to save your changes and return to the AOP page or 'Update and continue' to continue editing KE text sections.  The new text should appear under the “How It Is Measured or Detected” section on the AOP page.

I Biological Domain of Applicability for KE


Taxonomic Applicability for KE

Biological Domain of applicability is defined in the AOP-KB using a combination of structured fields and free text. Structured terms can  be selected to identify the taxa, life stage, sex, and the level of biological organisation (ex: cell, tissue or organ) for which the KE is known to be applicable. Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected from an ontology. In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE.

To add a taxonomic term to a KE page, under “Taxonomic Applicability” select ‘Add taxon.’ User will be directed to a page entitled “Add Taxonomic Term to Event.” The user can search for and select an existing term from the drop down list of existing terms to populate the “Term” field. Upon selection of a term, the Scientific term field will auto-populate. If a relevant term does not exist,  a new term may be requested via the 'Request new term' menu function. Click ‘Add taxonomic term’ to add this term to the AOP page. Evidence can be left blank and added later. The new term should be visible under the “Taxonomic Applicability.”

To edit a taxonomic term on a KE page, under “Taxonomic Applicability” click ‘Edit.’  User will be directed to a page entitled “Editing Event Taxon" where they can edit the Evidence field using the drop down menu. Clicking ‘Update taxonomic term’ will update the Evidence field and redirect the user back to the KE page.

To remove a taxonomic term on a KE page, under “Taxonomic Applicability” click ‘Remove.’ The record should no longer be visible under the “Taxonomic Applicability” heading on the KE page.

Life Stage Applicability for KE

Biological Domain of applicability is defined in the AOP-KB using a combination of structured fields and free text. Structured terms can  be selected to identify the taxa, life stage, sex, and the level of biological organisation (ex: cell, tissue or organ) for which the KE is known to be applicable.

To create a new life stage, on a KE page next to “Life Stages”, click ‘Add life stage term.’ This brings you to a page entitled, “New Event Life Stage” listing the Event name, with drop down options for Life stage term and Evidence fields. Evidence can be added later. Click ‘Create Event life stage’ to create a new life stage.  The new life stage should appear under the “Life Stage Applicability” section on the KE page.

To edit a life stage term on a KE page, under “Life Stage Applicability” click ‘Edit.’  User will be directed to a page entitled “Editing Event Life Stage" where they can edit the Evidence field using the drop down menu. Clicking ‘Update event life stage’ will update the Evidence field and redirect the user back to the KE page.

To remove a life stage term on a KE page, under “Life Stage Applicability” click ‘Remove.’ The record should no longer be visible under the “Life Stage Applicability” heading on the KE page.

Sex Applicability for KE

Biological Domain of applicability is defined in the AOP-KB using a combination of structured fields and free text. Structured terms can  be selected to identify the taxa, life stage, sex, and the level of biological organisation (ex: cell, tissue or organ) for which the KE is known to be applicable. The authors must select from one of the following: Male, female, mixed, asexual, third gender, hermaphrodite, or unspecific.

To edit the “Sex Applicability” section, on a KE page next to “Sex Applicability”, click ‘Add sex term.’ This brings you to a page entitled, “New Event Sex Term” listing the Event name, with drop down options for Term and Evidence fields. Evidence can be added later. Click ‘Create Event sex’ to create a new Event sex.  The Event sex should appear under the “Sex Applicability” section on the KE page.

To edit a sex term on a KE page, under “Sex Applicability” click ‘Edit.’  User will be directed to a page entitled “Editing Event Sex Term" where they can edit the Evidence field using the drop down menu. Clicking ‘Update event sex’ will update the Evidence field and redirect the user back to the KE page.

To remove a sex stage term on a KE page, under “Sex Applicability” click ‘Remove.’ The record should no longer be visible under the “Sex Applicability” heading on the KE page.

Evidence Supporting Applicability Domains for KE

This free text section should be used to elaborate on the scientific basis for the indicated domains of applicability and the WoE calls (if provided). The free-text section on evidence for taxonomic, life stage, and sex applicability can be used to elaborate on why the specific structured terms were selected, and provide supporting references and background information. 

To edit the "Domain of Applicability" section, on a KE page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Key Event.” Scroll down to the "Domain of Applicability"  section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update event’ to save your changes and return to the KE page.  The new text should appear under the "Domain of Applicability" section on the KE page.

J MIE-Specific Content


Stressors

This is a structured field used to identify specific agents (generally chemicals) that can trigger the KE. Stressors identified in this field will be linked to the KE in a machine-readable manner, such that, for example, a stressor search would identify this as an event the stressor can trigger. NOTE: intermediate or downstream KEs in one AOP may function as MIEs in other AOPs, meaning that stressor information may be added to the KE description, even if it is a downstream KE in the pathway currently under development.

To add a stressor associated with an MIE, under “Key Event Overview” click ‘Add Stressor’ will bring user to the “New Event Stressor” page. In the Name field, user can search for stressor by name. Results in the drop down menu are listed either as Stressors or Chemicals, with the caveat that selection of a Stressor may or may not create a record with an associated chemical, while selection of a Chemical term necessarily creates a record in the Chemical Table associated with that Stressor. Choosing a stressor from the resulting drop down populates the field. Users can add any supporting evidence in the Evidence text box. Click ‘Add stressor’ to add the stressor to the KE page. The stressor will be listed in the Stressors table.

To edit a Stressor, in the Stressors table next to the record you wish to edit, click the 'Edit' button. This will bring you to a new page entitled, "Editing Event Stressor" where you can modify the Evidence text. Click 'Update stressor' to save your changes. You will be returned to the Event page. To view the changes, click on the name of the Stressor will bring you to the individual Stressor page. Under the heading, "Event Evidence" you should see your updated evidence here.

To remove a Stressor, in the Stressors table next to the record you wish to edit, click the 'Remove' button. Click 'OK' and the record should no longer be present in the Stressors table.

Evidence for Perturbation of this MIE by Stressor

When a specific MIE can be defined (i.e., the molecular target and nature of interaction is known), in addition to describing the biological state associated with the MIE, how it can be measured, and its taxonomic, life stage, and sex applicability, it is useful to list stressors known to trigger the MIE and provide evidence supporting that initiation. This will often be a list of prototypical compounds demonstrated to interact with the target molecule in the manner detailed in the MIE description to initiate a given pathway (e.g., 2,3,7,8-TCDD as a prototypical AhR agonist; 17α-ethynyl estradiol as a prototypical ER agonist). Depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE).

To edit the “Evidence for Perturbation of This Molecular Initiating Event by Stressor” section, on an MIE page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Key Event.”  Scroll down to the “Evidence for Perturbation of This Molecular Initiating Event by Stressor” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update’ to save your changes and return to the MIE page or 'Update and continue' to continue editing KE text sections..  The new text should appear under the “Evidence for Perturbation of This Molecular Initiating Event by Stressor” section on the MIE page.

K AO-Specific Content


Regulatory Significance of the Adverse Outcome

A key criterion for defining an AO is its relevance for regulatory decision-making (i.e., it corresponds to an accepted protection goal or common apical endpoint in an established regulatory guideline study). For example, in humans this may constitute increased risk of disease-related pathology in a particular organ or organ system in an individual or in either the entire or a specified subset of the population. In wildlife, this will most often be an outcome of demographic significance that has meaning in terms of estimates of population sustainability.

To edit the “Regulatory Examples Using This Adverse Outcome” section, on an AO page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Key Event.”  Scroll down to the “Regulatory Examples Using This Adverse Outcome” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update’ to save your changes and return to the AO page or 'Update and continue' to continue editing KE text sections.  The new text should appear under the “Regulatory Examples Using This Adverse Outcome”  section on the AO page.

L Other Information


References

List of the literature that was cited for this KE description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).

To edit the “References” section, on a KE page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Key Event.” Scroll down to the “References” section, where a text entry box allows you to submit text. In the upper right hand menu, click ‘Update’ to save your changes and return to the KE page or 'Update and continue' to continue editing KE text sections.  The new text should appear under the “References” section on the KE page.

Comments and Discussion

See "Viewing and Commenting on AOPs" for instructions on how to comment or add to discussion on Key Events.

View History

See "View History" for details on how to view modifications to a KE page and revert to a previous version.

KE Watch list

The Watch List provides a list of individual AOP, KE, KER, or Stressor that a user is currently watching, similar to Bookmarks on an internet browser.

To add a page to the Watch List, navigate to the indivdual AOP, KE, KER, or Stressor page and in the upper right hand navigation menu, click 'Watch.' To remove a page from the Watch List, click 'Watch' to unselect the check box.