Long-Range Research Initiative - 2016-01-12 Ambit Guided Tourcefic-lri.org/wp-content/uploads/2015/09/AMBIT-guided... · 2018. 12. 12. · Ambit Guided Tour LRI Project EEM9.3 LRI

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LRI EEM9.3 TEAMCEFIC Long-range Research InitiativeCEFIC LRI Project EEM 9.315.01.2016

Ambit Guided Tour

LRI Project EEM9.3

LRI EEM9.3 TEAM, CEFIC Long-range Research Initiative, CEFIC LRI Project EEM 9.3, 15.01.2016

Introduction

Please note that this guided tour is not intended to give a full and comprehensive explanation of all Ambit functions.

The following main functionalities of Ambit are introduced in this document

– Search structures and associated data

– Search IUCLID substances by identifiers or endpoint data

– Import dataset and substance

– Assessment workflows: read across and category formation

– Toxtree prediction

It is important to note that every real chemical substance is not 100% pure. Therefore a substance should be characterised by its constituents, impurities and/or additives. The consequence is that a real chemical substance has NO structure, only each of its constituents, impurities and/or additives have a structure on its own.

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Relationship of structure and IUCLID Substance

IUCLID Substance ID & Composition

Every Substance in IUCLID is characterized by at least one composition

A Composition consists of

CONSTITUENTS n>= 1

IMPURITIES n>=0

ADDITIVES n>=0

A IUCLID substance itself has no chemical structure. Only constituents, impurities and additives have a structure

As a IUCLID composition has at least of 1 constituent, at least one structure is assigned. Most IUCLID substances are related to more than 1 structure

When the IUCLID composition is transferred, AMBIT assigns automatically searchable structures to constituents, impurities and additives (if they are available in the AMBIT structure pool of > 400.000 structures)


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Accessing Ambit

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Accessing AMBIT

Click hyperlink to open Ambit public server:

https://apps.ideaconsult.net/ambit3/


• Username & password will be provided by email


User interface


Menu items User info

Simple search box

Quick link

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Simple search


Simple Search


Simple search allows Google like quick access to structures.

Type in CAS No. or any other chemical identifier and press the Search button. The search results are displayed in the Structure search page (Fig below).

Example: type in the CAS No. 111-96-6

Screen with the search result

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Search structures and data


Search menu


The AMBIT search pages allow querying and retrieving chemical structures, substances and related data (examples see next slides):

• Search structures and associated data

• Exact, similarity, and substructure search

• Search IUCLID substances by identifiers

• Search IUCLID substances by endpoint data

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Search structures and associated data (1)General


Search structures and associated data in the following sequence:

1. Search for structure

Using identifiers like CAS No., name, etc. or structures drawn with an editor

2. Select structure from hit list

3. Display associated data


Search structures and associated data (1)Exact search - Search for structure


1. Click tab “Exact structure”

2. Insert search parameter

e.g. chemical identifier (SMILES, InChI, chemical name, CAS, EINECS) or a structure drawn by the structure diagram editor (icon 4, details see slide 21).

3. Initiate search

Click on spy glass (icon 3.)

1. 2. 3. 4.

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Search structures and associated data (1)Exact search - Select structure from hit list


Example: Exact search for “caffeine” results in the following hit list


Search structures and associated data (2)Exact search - Search for structure


Clicking “Enable Fragment search” checkbox allows to search for fragments in the Name field.

Example for fragment: 1,2-dichlor

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Search structures and associated data (3)Exact search - Display associated data


The folder icon (1) can be used to show “Identifiers” (2) of the structure or “Substances” (3) related to the structure.

The folder icon can be used to show or hide details about the chemical compound, or show/hide the lists of related substances.

2.

1.

3.

111-96-6




The Substances tab shows the 3 substances related to the chemical structure, and the role of the chemical structure (last column, e.g. Constituent, Impurity, Additive)

111-96-6

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Clicking the folder icon in the substance tab shows the detailed substance data e.g. Composition, Phys-chem. data, Environmental data, Ecotoxicity, and Toxicity.

Clicking on IUC-XXX link will open the same study tabs in a separate page, which might be more convenient

The content of the different tabs is shown on slides 27-29.

111-96-6


Search structures and associated data (8)Similarity search


Similarity search works only with structure information (SMILES, InChI, etc.) or names. Insert SMILES code, InChI or name in the search field or draw structure in structure diagram editor (see slide 21). The similarity search option retrieves chemical structures based on Tanimoto similarity. The default similarity threshold is 0.9 and can be selected through a dropdown box.

Example: insert SMILES “C1=CC=CC(/C=C/C2=CC=CC=C2)=C1” to search similar structures

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Search structures and associated data (8)Similarity search


The similarity search maybe limited to such structures where IUCLID substance data are available by clicking “Only hits with substances data”

From the hit list generated the desired structures and data can be displayed as shown under “exact search” see slide 15


Search structures and associated data (9)Substructure search


Substructure search

The substructure search query can be defined by drawing the structure (see next slide), selecting a SMARTS, or entering a SMARTS, SMILES or chemical name in the text box.

From the hit list generated the desired structures and data can be displayed as shown under “exact search” see slide 15.

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Search structures and associated data (10)


Structure draw

The structure editor can be toggled through the rightmost button on the search bar (the pen icon).

- To use the drawn structure for search, click the “Use” button.

- To show the structure, specified as SMILES in the search bar, click the “Draw” button.

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Search IUCLID substances by identifiers

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Search IUCLID substances by identifiersDisplay all IUCLID substances

Clicking the menu item “Search IUCLID substances by identifiers” retrieves all available IUCLID substances





Search with names:

Example: By inserting “diglyme” or “Glymes_Diethylene” into the field, the full hit list is reduced to the substance Diglyme, which has a name starting with the string.

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Search with names (regexp):

Example: By inserting “glyme” into the field “Name (regexp), the full hit list is reduced to 5 substances containing “glyme”.


Search IUCLID substances by identifiersDisplay of composition and associated structures

For display of a IUCLID substance composition and the associated structures, click folder symbol of substance.

When clicking on the “Substance UUID” link, the substance endpoint data will be displayed (see next slide)

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CompositionLink to endpoint data

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Substance page

– In the substance page, detailed substance data i.e. substance identifiers, composition, physicochemical, ecotoxicological, environmental date and toxicological properties are displayed under each tab.



Substance page – endpoint data (e.g. TOX)


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Substance page - Composition


– Under “Composition” page, the detailed composition data of the substance is displayed.

– Clicking “Also contained in…” button to find other substances which contain the specific structure as constituent, impurity, or additive (see next page)


Other substances containing formaldehyde


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Search IUCLID substances by endpoint data


Search IUCLID substances by endpoint dataThe available endpoints are listed on the left, grouped in four categories (P-Chem, Env Fate, Eco Tox, Tox).

Check one or more checkboxes (can be from several categories) and click the “Update results” button to show the substances, having the selected type of data. The endpoints are combined by “AND”.

It is also possible to search for values or ranges (see next slide)


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Search IUCLID substances by endpoint data

The folder icon at each endpoint row allows to set detailed search criteria for each endpoint.

All text boxes support autocompletion, i.e. the available values will be displayed and can be selected by either pressing an arrow down button (to list all available values) or by entering the first letters of a possible value.

e.g. Tox Endpoints


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Assessments

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AssessmentsMenu structure

– Comprehensive assessment workflows are developed for read-across and category formation based on all the data available in Ambit.

– The assessment workflow facilitates the search for target and source structures, generating data matrices, gap filling and generating assessment reports with predefined formats automatically


A “New assessment” can be generated by:

– “Use empty template”: to create a completely new assessment; all fields are empty.

– “Use existing assessment”: use the current available assessment in Ambit as a template.

The menu item ‘Existing assessment’ allows to access assessments for reading or editing purposes.

– “Own assessments”: the assessments generated by the logged in user

– “All assessments”: all assessment in Ambit


AssessmentsExisting assessments

– Under sub menu “ Existing assessments – All assessments/Own assessments”, the available assessments in Ambit are displayed.

– The assessments can be opened by clicking the “Assessment ID”

– The assessment can be searched by title or access rights


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Simplified work flowfor Assessments in AMBIT

Selecting data sources

Finalizing Assessment dataset

Selecting endpoints

Creating Assessment and defining initial target

Searching for target and source structures

Selecting relevant structures

Gap filling

Evaluation

Data gathering

Assessment StorageReport generation using predefined templates

Doc link

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AssessmentsWorkflow for read across and category formation


Assessment identifier Collect structures Endpoint data used Assessment details Report



Search substance(s) Selection of endpoints


Initial matrix Working matrix Final matrix


5 MAIN STEPS

7 SUB STEPS

The assessment workflow is organized in five main tabs. Some of the main tabs contain sub-tabs. The workflow goes from left to right in the main tabs as well as the sub-tabs. In principle, it should be not allowed to leave out any of the steps.

Collect structures List of collected structures

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AssessmentsNew assessment: Assessment identifier

– The Assessment identifiers need to characterize the Assessment also for later retrieval

– Fields marked with asterisk are mandatory; the others will be automatically generated by Ambit

– After input of the required identifiers, clicking “Start” to initiate the assessment


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AssessmentsCollect structure(s) (Target)

– Read across/category is an approach used to predict toxicity endpoint information for an untested chemical called target by using existing data from the same endpoint from another chemical(s) calledsource which is considered to be “similar” on the basis of molecular structure, chemical properties and/or other activities.

– The first step in the read across/category formation workflow is the search for the target/source.

– Search the target structure with “Exact search” (see slides 12-17).

– The identified target structure has to be marked as “T” (for target)

– The reason for each selection should be given in the field “Rationale”.


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AssessmentsCollect structure(s) (Source)

– Search source structure(s) by substructure or similarity search

– Check mark “Only hits with substance data” to find the structures with endpoints data only

– The relevant structures will be selected by marking as “S” (for source)

– The reason for each selection should be given in the field “Rationale”

– The source structures can be also searched manually by identifiers e.g. CAS No., Name, SMILES



AssessmentsList collected

– Under sub-menu of “List collected”, all the collected structures will be displayed, together with identifiers and rationale of selection


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AssessmentsEndpoint data used: Search substance(s)

– In this step, substance data can be searched and displayed for each structures collected by clicking the folder symbol.

– The relationship between the structure and substance is displayed in column “Contained in as”

– The relevant substance will be selected with a check mark ( √ )



AssessmentsEndpoint data used: Selection of endpoints

– Ambit shows the number of endpoints available for the selected substances.

– The assessor should check mark those endpoints which should be displayed in the data matrix.


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AssessmentsAssessment details

Forsake of clarity the data matrix is separate into 3 different sequential matrices, called “initial”, “working”, and “final”.

– “Initial Matrix”:

- Ambit generates automatically all available data in the “Initial matrix” and this matrix is read-only.

– “Working Matrix”:

- Clicking the button “Create working copy” generates a copy of the “Initial matrix” which can be edited.

- In this matrix, the assessor has to fill the data gaps by “estimates”, “external data sources”, “waivings”, “read-across”, “testing proposal”, etc.

- Ambit allows data filling and deleting data via pop up fields.

– “Final Matrix”

- Clicking the tab “Final matrix” generates a sanitized read-only version of the latest “Working matrix”.

- The “Final Matrix” displays a data matrix reduced to the minimum. All fields which are not necessary are no longer displayed.



AssessmentsAssessment details: Initial matrix

– All available substance data are listed in initial matrix

– The left side of the matrix contains the composition data of the selected substances together with the associated structures. The right side of the matrix contains the endpoint data

– For each data field, a hyperlink points to the IUCLID data in AMBIT


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AssessmentsAssessment details: Create working copy

– Click “Create working copy” to create the working matrix



AssessmentsAssessment details: Working matrix

– Empty data fields can be filled” via structured pop up window

– Pressing the “+” button to open the pop up window


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AssessmentsWorking matrix: Gap filling

– In the pop up window, the required field should be given by the assessor

– Press “Apply” button to transfer the inserted data in the working matrix



AssessmentsWorking matrix: Deleting data

– Inappropriate endpoint data for read across/category formation can be deleted by clicking the “-” sign. A pop up window opens where a rational for the deletion has to be given.

– All deleted endpoint data are marked in red.


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AssessmentsWorking matrix: Gap filling

– All inserted endpoint data are marked in red.

– After gap filling, press “Save” button to save current matrix



AssessmentsAssessment details: Create final matrix

– The final data matrix will be displayed under the sub tab “Final matrix” by refreshing this page.


Refresh web page in browser

− This “Final matrix” can not be edited any longer.

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AssessmentsAssessment details: Final matrix

– The final matrix is created based on the working matrix

– The final matrix will be included in the report



AssessmentsReport


A first version of the “Ambit Assessment Report” is available. The report can be downloaded as Word file.

It is also possible to generate Excel files of the initial and working matrix.

The report can be exported and documented as a Word file (.docx)

Ambit Assessment Report

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Toxtree Prediction in Ambit


Enhanced functionsRun Toxtree predictions

The “Enhanced functions ►Models ►Run Toxtree predictions” page combines a query page with user interface to run Toxtree models and display results for a single structure or multiple structures in a tabular mode

– A quick way to run Toxtree on all structures of an assessment is to provide URI of the structures for the assessment, e.g.

– https://apps.ideaconsult.net/ambit3/ui/toxtree?search=https://apps.ideaconsult.net/ambit3/bundle/35/compound


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Run Toxtree predictions


The Toxtree prediction results are stored in the database and can be collated with the search results through the search page sidebar, as described above.

1. Retrieve the structure

2. Run individual model

2. Automatically select all models and

run them all

The results will also automatically appear in the initial matrix as supporting info.

Documents

Long-Range Research Initiative - 2016-01-12 Ambit Guided Tourcefic-lri.org/wp-content/uploads/2015/09/AMBIT-guided... · 2018. 12. 12. · Ambit Guided Tour LRI Project EEM9.3 LRI