AMBIT Chemoinformatics Software for Data Management

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AMBIT Chemoinformatics Software for Data
Management

• Joanna Jaworska Nina Jeliazkova
• PG Brussels, Ideaconsult Ltd.,
• Belgium Bulgaria

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Introduction why Ambit ?

• Limited free, publicly accessible,
  methodologically transparent software was
  identified as one of the roadblocks for
  broadening use of in-silico methods (ICCA
  Workshop in Setubal 2002, OECD)
• Realization that efficient use of existing
  information on chemicals requires better ways for
  
• Storage
• standardized formats, computer automated
  verification of structures, capability to store
  large amounts of data
• Taking advantage of rapidly evolving field of
  data mining and extraction of relevant information

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IT strategy

• Ambit - building blocks for Decision Support
  System
• High emphasis on
• interoperability for plug and play
• Flexibility modular design
• Transparency
• Open source, relying on open standards. Open
  source software lowers the user barrier,
  facilitates the dissemination activities and
  enables the reproducibility of models and results
• The cheminformatics functionality relies on the
  open source Java library The Chemistry
  Development Kit http//cdk.sourceforge.net/
• The software is based on MySQL database
  (www.mysql.com), which is the most popular open
  source relational database.
• Chemical Markup Language (CML)
• acknowledged method of encoding chemical data in
  XML
• Is being adopted by a large number of chemical
  organisations, from government, through
  commercial to academia.
• The choice of CML for the internal format makes
  the database independent of the software which is
  able to access it, in contrast to some
  proprietary solutions.

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Ambit - Overview

• AMBIT software is a set of libraries and tools,
  providing various cheminformatics functionalities
  for data management.
• The AMBIT system consists of a database and
  functional modules allowing a variety of flexible
  searches and mining of the data stored in the
  database.
• The unique feature of AMBIT is the ability to
  store multifaceted information about chemical
  structures and provide a searchable interface
  linking these diverse components.

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Ambit overview

• The AMBIT database
• stores chemical structures, their identifiers
  such as CAS, INChI numbers attributes such as
  molecular descriptors, experimental data together
  with test descriptions, and literature
  references. The database can also store QSAR
  models. In addition the software can generate a
  suite of 2D and 3D molecular descriptors.
• can be searched by identifiers, attribute value
  or range, experimental data value or range, user
  defined structure and substructure, structural
  similarity
• AMBIT database contains over 450 000 chemical
  compounds with data imported from over a dozen
  databases http//ambit.acad.bg/ambit/stats/.
  The number of compounds is growing all the time
  and one the of systems great strengths is that
  any dataset can be imported for comparison and
  analysis. AMBITDatabaseTools 1.10 allows the user
  to create a local database and to import his own
  sets of chemical compounds.
• AMBIT Discovery performs chemical grouping and
  assesses the applicability domain of a QSAR
  offering a variety of methods including using
  different approaches to similarity assessments
  statistical that rely on descriptor space
  approaches based on mechanistic understanding
  and approaches based on structural similarity.
• ToxTree ToxTree is a flexible user friendly
  application which integrates structure based
  (classification) schemes. Currently 3 schemes are
  available Verhaaar for fish toxicity, Cramer for
  human acute toxicity, BfR rules for skin
  irritation. ToxTree implements a plug-in
  mechanism, allowing to be extended by modules
  developed at a future time, without recompiling
  the application. ToxTree and AMBIT modules can be
  integrated one within another.
• Toxmatch stand alone application for pairwise
  similarity assessments with intention for
  read-across.
• QSAR database under development. Will store
  information in QMRF. Large effort on
  standardization

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AMBIT Database Today
Not restricted to these datasets!Any dataset can
be imported. (e.g. DSSTox, AQUIRE, LLNA )
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AMBIT Database Schema
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Experimental results repository
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Ambit database

• Two user interfaces to the database
• Online
• Standalone
• Online
• a more restricted interface
• Standalone
• Full interface
• Can be used for storing managing confidential
  data
• Common
• Can link with other databases and pull
  information via webservices

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AMBIT database functionalities

• Storage information about chemicals name and
  structure, descriptors, experimental data and
  QSAR models
• Example with a tailored template BCF golden
  database LRI project ( EURAS) Q2 2007
• QSAR database with QMRF ( ECB funded)
• Conversion
• Different computer formats of structure,
  CAS-structure
• Calculation
• Variety of descriptors
• The available list is growing thanks to
  contributions to CDK
• Search
• identification search (CAS, SMILES, chemical
  name)
• Descriptor search
• Experimental data search
• Substructure and similarity search
• Complex searches with multiple criteria
  (standalone)

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What kind of searches are desired ?

• Detailed analyses for pairwise similarity
• Similarity of a compound to compounds in the
  database
• Similarity of a compounds to a reference set
• Similarity of a set of compounds to compounds in
  the database
• Grouping based on chemical class

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Ambit online

• Searching for basic information

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AMBIT OnlineSimilarity search replace with
new search results !!!
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AMBIT OnlineQuery result
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Links to other databases(example KEGG)
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Link to Aquire
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Information about QSAR models
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Ambit Database Tools 1.20Standalone
applicationavailable at http//ambit.acad.bg/down
loads
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Ambit converter (Batch search)

• Ambit converter can open CML, CSV, HIN, ICHI,
  INCHI, MDL MOL, MDL SDF, MOL2, PDB, SMI, TXT and
  XYZ file types
• Ambit converter can save SDF, MOL, CSV, TXT,
  SMI file types.
• CAS-SMILES conversion based on a database lookup
• Descriptors calculation
• Cramer rules,
• Verhaar scheme

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Ambit Database Tools 1.20

• Import to Database
• Compounds several file formats
• Descriptors SDF, CSV, TXT
• Experimental data SDF, CSV, TXT
• QSAR models SDF, CSV, TXT

• Database processing
• Calculate SMILES/Fingerprints/Atom environments
  necessary in order to perform substructure and
  similarity search. Should be invoked after
  importing compounds into database
• several file formats
• Descriptors calculation
• Distances calculation used to speed up distance
  between heavy atoms query

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Ambit Database Tools 1.20

• perform a CAS RN search in the database (submenu
  "Search -gt CAS RN search")
• perform a SMILES search in the database (submenu
  "Search -gt SMILES")
• perform a molecular formula search in the
  database (submenu ("Search -gt Molecular
  formula")
• define structure,descriptor,distance-based and
  experimental data criteria and perform searches
  in the database database

• Output
• On screen
• To file

The user can select between the different
datasets existing in the AMBIT database.
Subsequent searches will be performed only
within the selected dataset
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AMBIT User InterfaceExample Search by structure

• Exact search
• Substructure search
• Similarity search
• Fingerprints
• Atom environments

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AMBIT User InterfaceExample Search by
descriptors
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AMBIT User InterfaceExample Search by
experimental data
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Similarity based on toxicity mechanismVerhaar
scheme Verhaar H.J.M., Van Leeuven C., Hermens
J.L.M.,Classifying Environmental Pollutants. 1
Structure-Activity Relationships for Prediction
of Aquatic Toxicity, Chemosphere, Vol.25, No.4,
pp.471-491, 1992

• 34 rules
• 5 classes
• Class 1. Narcosis or baseline toxicity
• Class 2 Less inert compounds
• Class 3 Unspecific reactivity
• Class 4 Compounds and groups of compounds acting
  by a specific mechanism
• Class 5 Not possible to classify according to
  these rules

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Chemical similarity assessment using the database

• Exact substructure search based on 2D
• Structural Similarity search (various methods)
• Criteria on descriptors
• Based on mechanistic understanding ( Verhaar
  scheme)

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Another view on Similarity assessments with
Toxmatch and Discovery

• Discovery
• similarity to a set (summary representation)
• Toxmatch
• pairwise similarities
• Similarity to a set (nearest neighbours)

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Thank you
Questions?