Help: AOPs

A Create a new AOP


Identifier

Each AOP is automatically given a numerical AOP identifier when it is created.

Title

Each AOP should be given a descriptive title that takes the form “MIE leading to AO”. For example, “Aromatase inhibition [MIE] leading to reproductive dysfunction [AO]” or “Thyroperoxidase inhibition [MIE] leading to altered neurodevelopment [AO]”. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE.

On the ‘AOP’s’ page, upon selecting the “New AOP” button, the user will see a ‘New AOP’ form with fields for the entry of a ‘Title’ and a ‘Short name.’ The long title should be of the form described above. Upon entering a Title and a Short Name, click 'Create AOP' to save the new AOP.

Short name

A short name should also be provided that succinctly summarises the information from the title. This name should not exceed 90 characters.

B Graphical Representation of the AOP


Graphical Representation

A graphical summary of the AOP listing all the KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs should be provided. The graphical representation, or AOP diagram provides a useful and concise overview of the KEs that are included in the AOP, and the sequence in which they are linked together. This can aid both the process of development, as well as review and use of the AOP.

If you already have a graphical representation of your AOP in electronic format, simple save it in a standard image format (e.g. jpeg, png) then click ‘Choose File’ under the “Graphical Representation” heading, which is part of the "Summary of the AOP" section, to select the file that you have just edited. Files must be in jpeg, jpg, gif, png, or bmp format. Click ‘Upload’ to upload the file. You should see the AOP page with the image displayed under the “Graphical Representation” heading. To remove a graphical representation file, click 'Remove' and then click 'OK.'  Your graphic should no longer be displayed on the AOP page. 

If you do not have a graphical representation of your AOP in electronic format, a template is available to assist you.  Under “Summary of the AOP”, under the “Graphical Representation” heading click on the link “Click to download template for graphical representation.” A Powerpoint template file should download via the default download mechanism for your browser. Click to open this file; it contains a Powerpoint template for an AOP diagram and instructions for editing and saving the diagram. Be sure to save the diagram as jpeg, jpg, gif, png, or bmp format. Once the diagram is edited to its final state, upload the image file as described above.

C Authors of AOP


Authors and Affiliations

List the name and affiliation information of the individual(s)/organisation(s) that created/developed the AOP. In the context of the OECD AOP Development Workplan, this would typically be the individuals and organisation that submitted an AOP development proposal to the EAGMST. Significant contributors to the AOP should also be listed. A corresponding author with contact information may be provided here. This author does not need an account on the AOP-KB and can be distinct from the point of contact below. 

To add or edit authors, click Edit in the upper right hand menu on the AOP page, bringing the user to a page where they can edit fields of the AOP.  Under the “Authors” heading, enter authors’ names in the text box.  Upon completion, click ‘Update’ in the upper right hand menu to update the list of Authors.

Point of Contact

Indicate the point of contact for the AOP-KB entry itself, this person is responsible for managing the AOP entry in the AOP-KB and controls write access to the page by defining the contributors as described below. Clicking on the name will allow any wiki user to contact the point of contact via the email address associated with their user profile in the AOP-KB. This person can be the same as the corresponding author listed in the authors section but isn’t required to be. 

Click Edit in the upper right hand menu on the AOP page, bringing the user to a page where they can edit fields of the AOP.  Under the "Point of Contact" heading, click the arrow to bring up a dropdown menu populated with the list of contributors. Select a contributor from the list, upon selection this person becomes the Point of Contact. Click 'Update' in the upper right-hand menu to save your changes.  The new Point of Contact should appear under the "Point of Contact” heading on the AOP Page.

 

 

Contributors

List user names of all  authors contributing to or revising pages in the AOP-KB that are linked to the AOP description. This information is mainly used to control write access to the AOP page and is controlled by the Point of Contact.

Click Edit in the upper right hand menu on the AOP page, bringing the user to a page where they can edit fields of the AOP.  Under the Contributors heading, you should see the names of existing Contributors. To add a new contributor, click ‘Add Contributor’ to bring up a new page entitled "New Contributor" with a dialog box searchable by last name.  Search for and select the person you wish to add, then click 'Add contributor.' Upon adding a contributor, you will be returned to the Editing AOP page. In the upper right hand menu, click ‘Update’ to save your changes. Upon successful submission, the new contributor’s name should appear under the “Contributors” heading.

D Status of an AOP


Author status

The status section is used to provide AOP-KB users with information concerning how actively the AOP page is being developed, what type of use or input the authors feel comfortable with given the current level of development, and whether it is part of the OECD AOP Development Workplan and has been reviewed and/or endorsed. 

To edit the Status, click Edit in the upper right hand menu on the AOP page. Under “Status,” select a status from the drop down list of options. In the right hand menu, click ‘Update AOP’ to change the status. You will be returned to the AOP page, where the Author status record in the Status table will be updated. 

OECD Status

For AOPs that are included in a project that has been accepted into the OECD AOP Development Workplan (see http://www.oecd.org/chemicalsafety/testing/projects-adverse-outcome-pathways.htm), status with regard to progress through OECD review and endorsement processes is tracked by the OECD EAGMST. ‘OECD status’ tracks the level of review/endorsement the AOP has been subjected to. This designation is managed and updated by the OECD. It is not selected by the AOP author(s).

OECD Project Number

The OECD project number is also indicated along with the current status of the AOP with regard to the OECD workplan. This designation is managed and updated by the OECD. It is not selected by the AOP author(s).

SAAOP Status

All AOPs under development in the AOP-KB are monitored by curators (also referred to as gardeners) who are members of the Society for the Advancement of AOPs (SAAOP). These gardeners maintain a separate status designation for AOPs based on their evaluation of the current state of the AOP. These designations are managed and updated by the SAAOP gardeners. They are not selected by the AOP author(s). 

History of Modifications

Indicates the date (day/month/year) of any update of the AOP. The date and time of all entries and revisions to the wiki are tracked automatically. The last modification date for the AOP will show under the Status heading. The Revision Table also shows the modification dates for the related pages covering key events, key event relationships, and stressors and can be viewed by clicking on the link “Click here to show/hide revision dates for related pages.” A more detailed history is available for any page by clicking the "View History" button in the top right of the page, see detailed instructions here

E AOP Abstract


Abstract

In the abstract section, authors should provide a concise and informative summation of the AOP under development that can stand-alone from the AOP page. Abstracts should typically be 200-400 words in length (similar to an abstract for a journal article). Suggested content for the abstract includes the following: (1) the background/purpose for initiation of the AOP’s development (if there was a specific intent); (2) a brief description of the MIE, AO, and/or major KEs that define the pathway; (3) a short summation of the overall WoE supporting the AOP and identification of major knowledge gaps (if any); (4) if  a brief statement about how the AOP may be applied (optional). The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance.

To add or edit the Abstract, click Edit in the upper right hand menu on the AOP page, bringing the user to a page where they can edit fields of the AOP. Under the Abstract field, a text editable form provides ability to edit the Abstract.  Clicking ‘Update AOP’ will update these fields or 'Update and continue' to continue editing AOP text sections.

F Background Information


Background (optional)

This optional subsection should be used to provide background information for AOP reviewers and users and it is considered helpful in understanding the biology underlying the AOP and the motivation for its development. The background should NOT provide an overview of the AOP, its KEs or KERs,

To add background information, click Edit in the upper right hand menu on the AOP page. Under the “Background (optional)” field, a text editable form provides ability to edit the Background.  Clicking ‘Update AOP’ will update these fields or 'Update and continue' to continue editing AOP text sections.

G KE and KER Tables


Summary

This section is for information that describes the overall AOP. The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed.

Molecular Initiating Event

An MIE is a specialised KE that represents the beginning (point of interaction between a stressor and the biological system) of an AOP.

To add a molecular initiating event to an AOP page, under Summary of the AOP, click ‘add molecular initiating event.’ User will be brought to a new page entitled ‘Add Event to AOP.’ Entering text into the Title field will bring a drop-down list of already existing MIE’s. If the user wishes to create a new MIE that doesn’t already exist, they should type in the name of the MIE without selecting a choice from the drop down menu. User should fill Title, Short name, Biological organization fields and click ‘Create Molecular Initiating event.’ This brings user back to the AOP page with updated MIE under the heading “Molecular Initiating Event.” To remove a molecular initiating event from an AOP page, under Summary of the AOP, under the heading "Molecular Initiating Event", click ‘Remove.’

Key Events

This table summarises all of the KEs of the AOP. This table is populated in the AOP-Wiki as KEs are added to the AOP. Each table entry acts as a link to the individual KE description page. 

To add a key event to an AOP page, under Summary of the AOP, click ‘add key event.’ User will be brought to a new page entitled ‘Add Event to AOP.’ Entering text into the Title field will bring a drop-down list of already existing KE’s. If the user wishes to create a new KE that doesn’t already exist, they should type in the name of the KE without selecting a choice from the drop down menu. User should fill Title, Short name, and Biological organization fields and click ‘Add/Create Key event.’ This brings user back to the AOP page with updated record in the table under the heading “Key Events.”

To remove a key event from an AOP page, under Summary of the AOP, under the heading "Key Events", click ‘Remove.’

Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. 

To add an adverse outcome to an AOP page, under Summary of the AOP, click ‘add adverse outcome.’ User will be brought to a new page entitled ‘Add Event to AOP.’ Entering text into the Title field will bring a drop-down list of already existing KE’s. If the user wishes to create a new AO that doesn’t already exist, they should type in the name of the AO without selecting a choice from the drop down menu. User should fill Title, Short name, and Biological organization fields and click ‘Create Adverse Outcome.’ This brings user back to the AOP page with updated record in the table under the heading “Adverse Outcome.”

To remove an adverse outcome from an AOP page, under Summary of the AOP, under the heading "Adverse Outcome", click ‘Remove.’

Relationships Between Two Key Events

This table summarises all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP. Each table entry acts as a link to the individual KER description page.

To add a key event relationship to an AOP page, under Summary of the AOP, next to “Relationships Between Two Key Events (Including MIEs and AOs)” click ‘Add relationship.’ User will be brought to a new page entitled ‘Add Relationship to AOP.’ To create a new relationship, select an upstream event and a downstream event from the drop down menus. Select a Directness from the drop down menu. The fields “Evidence” and “Quantitative understanding” can be entered at the time of creation of the relationship, or can be added later. Upon selection of these options from their respective drop-down menus, click ‘Create Aop relationship.’ The new relationship should be listed on the AOP page under the heading “Relationships Between Two Key Events (Including MIEs and AOs)”.

To edit a key event relationship, click ‘Edit’ next to the name of the relationship you wish to edit. The user will be directed to an Editing Relationship page where they can edit the Directness, Evidence, and Quantitative Understanding fields using the drop down menus. Once finished editing, click ‘Update Aop relationship’ to update these fields and return to the AOP page.

To remove a key event relationship to an AOP page, under Summary of the AOP, next to “Relationships Between Two Key Events (Including MIEs and AOs)” click ‘Remove relationship.’ The relationship should no longer be listed on the AOP page under the heading “Relationships Between Two Key Events (Including MIEs and AOs)”.

H AOP Networks


Network View

The AOP-Wiki automatically generates a network view of the AOP. This network graphic is based on the information provided in the MIE, KEs, AO, KERs and WoE summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs.

The network view is automatically generated upon addition of events and relationships to an AOP page. To move the nodes of the network, click on a node and drag it to the desired location in the View. Double-clicking on the node will free it once more. Hovering over a node will display the Event or Relationship number and its title at the bottom of the View. Clicking on the title will direct you to that Event or Relationship page.

To view the events/relationships by name, click ‘Show names’ under the Network View. To view events/relationships by ID, click ‘Show IDs’ to return to that view of the Network.

To reveal/hide AOPs related to the KEs in the relationship, click 'Show AOPs' to reveal and 'Hide AOPs' to hide.

To reveal/hide Non-adjacent relationships, click 'Show nonadjacent' or 'Hide nonadjacent.'

To reset the original positions of the events in the Network View, click 'Reset positions.'

I Stressors and Applicability Tables


Stressors

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, 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). It can also include non-chemical stressors such as genetic or environmental factors. 

To add a stressor associated with an AOP, under “Summary of the AOP” click ‘Add Stressor’ will bring user to the “New Aop Stressor” page. In the Name field, user can search for stressor by name. Choosing a stressor from the resulting drop down populates the field. Typing a new stressor name will allow the user to add a new stressor that is not already existing. Selection of an Evidence level from the drop down menu and add any supporting evidence in the text box. Click ‘Update stressor’ to add the stressor to the AOP page, where it should appear as a new record in the table under the "Stressors" heading.

The Evidence and Evidence text fields may also be added later. To edit these fields, on the AOP page, next to the stressor that you wish to edit, click 'Edit.' This will bring you to a page entitled, "Editing AOP stressor." Edit the Evidence and Evidence text fields and click ‘Update stressor’ to save your changes.  You will be returned to the AOP page. To view the changes, click on the name of the Stressor will bring you to the individual Stressor page. Under the heading, "AOP Evidence" you should see your updated evidence here.

To remove a Stressor on an AOP page, under “Stressors” click ‘Remove.’  Click 'OK' and the term should no longer be visible under the  “Stressors” heading.

Life Stage Applicability

Identify the life stage for which the KE is known to be applicable.

To add a life stage term to an AOP page, under “Life Stage Applicability” click ‘Add life stage term.’ User will be directed to a page entitled “Add Life Stage to AOP.” This page will list the AOP name, with drop down menu options to select a Life Stage term and Evidence. Evidence can be left blank and added later. Click 'Create Aop life stage' to add the life stage term to the AOP. The new term should be viewable in the table under the  “Life Stage Applicability” heading on the AOP page.

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

To remove a life stage term on an AOP page, under “Life Stage Applicability” click ‘Remove.’  Click 'OK' and the term should no longer be visible under the  “Life Stage Applicability” heading.

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected. 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 an AOP page, under “Taxonomic Applicability” select ‘add taxonomic term.’ User will be directed to a page entitled “Adding Taxonomic Term to AOP.” The user can search for and select an existing term from the drop down list of existing terms to populate the “Term” field. The "Scientific Name" field is immediately populated upon selection of a common name. If a relevant term does not exist, it may be requested using the ’request new term' functionality to request a term from AOP-Wiki administrators. Evidence may be left blank and added later. Click ‘Add taxonomic term’ to add this term to the AOP page. A new record should appear in the “Taxonomic Applicability” table on the AOP page.

To edit a taxonomic term on an AOP page, under “Taxonomic Applicability” click ‘Edit.’  User will be directed to a page entitled “Editing AOP Taxonomic Term” 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 AOP page.

To remove a taxonomic term on an AOP page, under “Taxonomic Applcability” click ‘Remove.’  Click 'OK' and the “Taxonomic Applicability” table on the AOP page should no longer display the term.

Sex Applicability

The authors must select from one of the following: Male, female, mixed, asexual, third gender, hermaphrodite, or unspecific.

To add a sex term to an AOP page, under “Sex Applicability” select ‘Add sex term.’ User will be directed to a page entitled “Add Sex Term to AOP.” The user can select a Sex Term and Evidence from the drop down list and click 'Create AOP Sex' to add this term to the AOP page. Evidence may be left blank and added later.

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

To remove a sex term on an AOP page, under “Sex Applicability” click ‘Remove’ then click 'OK.'  The AOP page will be displayed without the term under the “Sex Applicability” heading.

J Overall Assessment of the AOP


Overall Assessment Summary

This section addresses the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and WoE for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). The goal of the overall assessment is to provide a high level synthesis and overview of the relative confidence in the AOP and where the significant gaps or weaknesses are (if they exist). Users or readers can drill down into the finer details captured in the KE and KER descriptions, and/or associated summary tables, as appropriate to their needs.

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

A supporting .pdf file may also be added to the Overall Assessment section. To upload a file, under the “Overall Assessment of the AOP” section click 'Choose File' to bring up a dialog window where you can select a file to upload. Click 'Open' to select a file and return to the AOP page. Then click 'Upload' to attach the file to the AOP page. You should see "Attached file: [filename]". Clicking on the filename will open a new window displaying the pdf you have uploaded.  

To remove a file, click 'Remove' and then 'OK.' The AOP page should be displayed with “Overall Assessment of the AOP” no longer displaying the filename.

Biological Domain of Applicability

The relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context are defined in this section.

To edit the “Domain of Applicability” section, on an AOP page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing AOP.” 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 AOP’ to save your changes and return to the AOP page or 'Update and continue' to continue editing AOP text sections.  The new text should appear under the “Domain of Applicability” section on the AOP page.

Essentiality of the Key Events

An important aspect of assessing an AOP is evaluating the essentiality of its KEs. The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence.

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

Evidence Assessment

The biological plausibility, empirical support, and quantitative understanding from each KER in an AOP are assessed together.  Biological plausibility of each of the KERs in the AOP is the most influential consideration in assessing WoE or degree of confidence in an overall hypothesised AOP for potential regulatory application (Meek et al., 2014; 2014a). Empirical support entails consideration of experimental data in terms of the associations between KEs – namely dose-response concordance and temporal relationships between and across multiple KEs. 

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

Quantitative Considerations

Specific attention is also given to how precisely and accurately one can potentially predict an impact on KEdownstream based on some measurement of KEupstream. This is captured in the form of quantitative understanding calls for each KER.

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

K Other AOP Information


Considerations for Potential Applications of the AOP (optional)

At their discretion, the developer may include in this section discussion of the potential applications of an AOP to support regulatory decision-making. This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. While it is challenging to foresee all potential regulatory application of AOPs and any application will ultimately lie within the purview of regulatory agencies, potential applications may be apparent as the AOP is being developed, particularly if it was initiated with a particular application in mind. This optional section is intended to provide the developer with an opportunity to suggest potential regulatory applications and describe his or her rationale.

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

References

List the bibliographic references to original papers, books or other documents used to support the AOP.

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

Snapshots

For further background and instructions regarding Snapshots, please see the linked Help page.

Comments and Discussion

See here for further instructions on how to comment and contribute to discussion.

View History

To view detailed changes to an AOP, KE, KER, or Stressor page, click 'View History' on the upper right hand panel menu on the page. You will be brought to a page entitled "Versions of [AOP/KE/KER/Stressor:#]" listing text changes to the AOP/KE/KER/Stressor by date. To compare two versions, select the versions you would like to compare using the "from" and "to" buttons.  Click 'Compare.' You will be brought to a page showing the comparison of the two versions. If you are a contributor to this AOP, you can also click 'revert to this version' at the bottom of the page to revert to a previous version of an AOP/KE/KER/Stressor.

The Change log lists all changes to an AOP/KE/KER/Stressor including text changes, the date and the user who made the change.

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.