CEFIC LRI Project EEM9.3 Linking LRI AMBIT Chemoinformatic System - - PowerPoint PPT Presentation

▶
cefic lri project eem9 3
SMART_READER_LITE
LIVE PREVIEW

CEFIC LRI Project EEM9.3 Linking LRI AMBIT Chemoinformatic System - - PowerPoint PPT Presentation

Feb 07, 2024 32 likes •455 views

17 th Annual CEFIC-LRI Workshop 20 15 CEFIC LRI Project EEM9.3 Linking LRI AMBIT Chemoinformatic System with the IUCLID Substance Dr. Volker Koch, Clariant CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015 Database to

slide-1
SLIDE 1

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

CEFIC LRI Project EEM9.3

Linking LRI AMBIT Chemoinformatic System with the IUCLID Substance Database to Support Read across of Substance Endpoint data & Category Formation

17th Annual CEFIC-LRI Workshop 20 15

slide-2
SLIDE 2

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

Introduction

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

2

slide-3
SLIDE 3
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Computational Toxicology (1)

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

3

  • Non-testing approaches are used to fill gaps in Hum an and

Environm ental Safety Assessm ent (ECETOC, 20 12 TR116) :

  • To avoid animal testing
  • Reduce resource costs
  • Bridge the gap of laboratory capacity availability
  • Read-across and Category form ation
  • Are Non-testing methods which are regularly applied to assess the safety of

Chemicals and are accepted by most Regulatory Bodies if the approach taken is sufficiently justified and documented

  • Is supported by in-silico tools (see ECETOC, 2012, TR 116) using various

methodologies like

  • QSARs, Expert systems allowing rule-based predictions , Similarity tools etc.
slide-4
SLIDE 4
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Computational Toxicology (2)

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

4

  • MAJOR GOALS OF THE CEFIC LRI PROJECT
  • Enhancing the predictive power of the in-silico tool LRI

AMBIT

  • Using high quality Substance data
  • From a IUCLID Database owned by a company itself
  • From ECHA IUCLID Database (non-CBI Disseminated data)
  • From other reliable and quality checked data sources
  • Im plem enting workflows for Assessm ents

supporting the assessor in setting up a read across/ category approach and in establishing a valid justification for the approach taken as requested by authorities

  • Minim izing overall anim al testing and resource costs

means using available studies for other substances as well if appropriate

slide-5
SLIDE 5
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Project overview

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

5

Com pany IUCLID DB ECHA IUCLID DB As Major Data Source Search for data possible but not for structures CEFIC LRI AMBIT Chem oinform atics System Supporting Read across & Category form ation AMBIT FUNCTIONS Assigning structures

  • to constituents, impurities …

Search structures & Data

  • exact, similar, substructure
  • combined with data search

Read across/category formation

  • Workflows supporting the user

Prediction tools

  • Cramer rules, Protein binding etc

Data analysis tools

  • Regressions, clustering etc.

Data management

  • flexible import/export of data

Data exchange

  • manual or automated e.g.

webservices Data transfer

slide-6
SLIDE 6

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

IUCLID Data handling, Retrieval & Export

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

6

slide-7
SLIDE 7
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Database

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

7

IUCLID Version 4 IUCLID Version 5 Many page scrolls IUCLID 4 had ca. 8 50 Database fields IUCLID 5 has > 8 50 0 Database fields Manual Extraction of substance data to be used in read across/category is cumbersome & time consuming Manual Extraction of substance data to be used in read across/category is rather straightforward

slide-8
SLIDE 8
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance ID & Composition

  • IUCLID Substance ID & Com position
  • Every Substance in IUCLID is characterized by at least one Com position
  • A IUCLID Substance com position has
  • CONSTITUENTS n>= 1, IMPURITIES n>=0 , ADDITIVES n>=0
  • A IUCLID substance itself has NO CHEMICAL STRUCTURE.

Only constituents, im p urities a nd a d d itiv es ha v e a structure

  • As a IUCLID composition has at least 1 constituent, at least one structure is
  • assigned. Very m any IUCLID substances are related to m ore than 1

structure

  • When the IUCLID com position is transferred, AMBIT assigns

autom atically searchable structures to constituents, im purities and additives (if they are available in the AMBIT structure pool of > 400.000 structures)

  • Most in-silico tools e.g. the OECD Toolbox cannot cope with the

com position of a substances and relates one structure to a substance !

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

8

slide-9
SLIDE 9
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Data retrieval in IUCLID 5 (1)

  • Endpoint data in IUCLID can be retrieved
  • “Manually”
  • if location is known by the user
  • Using the IUCLID Query Tool
  • Requires knowledge about the IUCLID data structure (experts only)
  • Structures in IUCLID are
  • Images which cannot be retrieved
  • Sm iles codes which can be used for exact structure search only but not

for sim ilarity or substructure search

  • Not directly applicable for read across/ category form ation approaches

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

9

slide-10
SLIDE 10
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Methods for Data transfer from IUCLID to AMBIT

  • Manual Transfer
  • Using the IUCLID 5 Bulk Export Assistant which is cumbersome requiring a

multistep and manual interaction

  • Using the IUCLID 5 Batch Export which also requires a limited manual

interaction

  • Autom ated Transfer using Web services
  • IUCLID 5 and AMBIT are IT system which are running on Web servers
  • Web servers can interact via Web services allowing autom ated data

transfer and update from IUCLD 5 not requiring manual interaction

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

10

slide-11
SLIDE 11

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

AMBIT Data import

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

11

slide-12
SLIDE 12
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Data Import filter for AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

12

  • These filter allow to select which data from an IUCLID substance should be

imported into AMBIT and work for manual or web based data import from IUCLID

slide-13
SLIDE 13

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

AMBIT Chemoinformatics System

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

13

Data & Structure handling Functions Communication

slide-14
SLIDE 14
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

LRI AMBIT Chemoinformatic System

  • AMBIT Chem oinform atics System was developed within a CEFIC LRI

Project in 2005 and is part of the LRI Toolbox

  • Was continuously developed further and is now a state of the art Java web

application running on all Operating Systems supporting Java

  • Is an Open Source Application with the following functions
  • Search for structure(s) [exact, similar, substructure] and m eta data
  • Assessm ent tools (read across/ category form ation)
  • Prediction tools e.g. Cramer rules , Protein binding, pKa etc
  • Data analysis tools e.g. regression, classification, clustering etc
  • Data exchange tools: manual or automated via Opentox API, Webservices etc

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

14

slide-15
SLIDE 15
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

AMBIT Search for Structures

Exact, Sim ilarity & Substructure

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

15

slide-16
SLIDE 16
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

AMBIT Search for Structures & Endpoint data

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

16

2) Find Substance(s) 3) Display data 1) Find Structure(s)

slide-17
SLIDE 17
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Structures of Constituents, Impurities, Additives

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

17

slide-18
SLIDE 18
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance Data in AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

18

  • IUCLID Data in AMBIT are organized in tab sections allowing

easy access by clicking on the tab of interest

slide-19
SLIDE 19
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance Data in AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

19

  • IUCLID Composition Data in AMBIT allow a straightforward
  • verview on constituents, impurities & additives as well as the

concentrations associated

slide-20
SLIDE 20
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance Data in AMBIT Data for 44 Endpoints from IUCLID

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

20

slide-21
SLIDE 21
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance Data in AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

21

slide-22
SLIDE 22
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance Data in AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

22

slide-23
SLIDE 23
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance Data in AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

23

slide-24
SLIDE 24
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

IUCLID Substance Data in AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

24

slide-25
SLIDE 25

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

AMBIT Chemoinformatics System

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

25

Communication with other Systems

slide-26
SLIDE 26
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

AMBIT Communication

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

26

Other Tools Other Databases Com pany Database Batch transfer End 2015 Transfer via Web service

  • r manually
slide-27
SLIDE 27

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

Workflow Read across & Category formation

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

27

slide-28
SLIDE 28
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Selecting data sources Finalizing Assessment dataset Selecting endpoints

Creating Assessment and defining initial target Searching for other targets and allied structures

Selecting relevant structures Gap filling Evaluation Data gathering Assessment Storage

Report generation using predefined templates

Doc link

28

Maybe iterative process

AMBIT Workflows on Read across & Category formation

slide-29
SLIDE 29
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

New Assessment & Identifier

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

29

slide-30
SLIDE 30
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Collect (Search) structures for Assessment

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

30

T = Target, S = Source, CM = Category member

  • Based on the Sm iles code of the Target Diglym e a substructure search

was carried out lim ited to those having substance data

  • Clicking T, S or CM allows to assign the structure for intended purpose
slide-31
SLIDE 31
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

List collected structures for Assessment

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

31

T = Target, S = Source, CM = Category member

  • Based on the Sm iles code of the Target Diglym e a substructure search

was carried out lim ited to those having substance data

slide-32
SLIDE 32
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Search Substances

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

32

  • When clicking the Tab “Endpoint data used” associated substances can be

display from the list and selected for further use (Subtab “Search substance(s)”)

slide-33
SLIDE 33
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Search Substances

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

33

  • When clicking the Tab “Endpoint data used” and subsequently Subtab

“Selection of endpoints” a list of IUCLID Endpoints are displayed for selection by check marking

slide-34
SLIDE 34
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Working matrix (Composition section)

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

34

slide-35
SLIDE 35
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Working matrix (Endpoint section)

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

35

slide-36
SLIDE 36
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

EXCEL Export of Working Matrix

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

36

  • AMBIT has several reporting functions, one is the export of the Working matrix

into EXCEL for easier handling and printing

slide-37
SLIDE 37
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Assessment report

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

37

  • AMBIT has several reporting functions, one is creating an assessment report in

Word

slide-38
SLIDE 38

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

Project information

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

38

Project will be finalized on December 8, 2015

slide-39
SLIDE 39
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Project information

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

39

  • Project idea

Volker Koch, Clariant

  • LRI Manager

Bruno Hubesch

  • Contractors

Nina Jeliazkova, Ideaconsult Ltd Egon Willighagen, Maastricht University

  • Clariant Team

Udo Jensch, Toxicologist for System design Volker Koch, Ecotoxicologist Qiang Li, Toxicologist Joachim Schneider-Reigl, Ecotoxicologist

  • Project end

Decem ber 8 , 20 15

slide-40
SLIDE 40

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

System requirements for AMBIT

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

40

slide-41
SLIDE 41
  • Dr. Volker Koch, Clariant, CEFIC LRI Annual Workshop 2015, CEFIC LRI Project EEM9.3, 19.11.2015

Installation

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

41

  • AMBIT is an Open Source Web Application and can be used free
  • f charge when accepting the LGPL license
  • Requirem ents

Java 7, MySQL Database,Web server (servlet container, e.g. Apache Tomcat )

  • LOCAL on a LAPTOP/ DESKTOP

local database, local webserver, manual data import. Data update is complicated.

  • SERVER (on com pany INTRANET)

Shared database and web server. Clients only need a web browser.

  • Publicly available

https://apps.ideaconsult.net/ambit3 Clients only need a web browser.

  • TECHNICAL SUPPORT

contact Ideaconsult Ltd, Sofia (see Flyer distributed in this meeting) w w w .ideaconsult.net , em ail: support@ideaconsult.net

slide-42
SLIDE 42

Public

  • Dr. Volker Koch, Clariant

CEFIC LRI Annual Workshop 2015 CEFIC LRI Project EEM9.3 19.11.2015

CEFIC LRI Workshop on Project EEM9.3 Linking AMBIT with IUCLID

Public, LRI PROJECT EEM9.3LINKING AMBIT WITH IUCLID

42

Date January 21, 2016 Location CEFIC Premises Brussels Registration starting now send E Mail to bhu@cefic.be