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CEFIC LRI Tools – Ambit 1.21

CEFIC LRI Tools – Ambit 1.21. Nina Jeliazkova Ideaconsult Ltd. Sofia, Bulgaria. Outline. Ambit overview Demo : Finding basic information about a query compound in the database Complex query in the database –retrieve data meeting multiple criteria from Ambit database

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CEFIC LRI Tools – Ambit 1.21

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  1. CEFIC LRI Tools – Ambit 1.21 Nina Jeliazkova Ideaconsult Ltd. Sofia, Bulgaria

  2. Outline • Ambit overview • Demo : • Finding basic information about a query compound in the database • Complex query in the database –retrieve data meeting multiple criteria from Ambit database • Import data from EURAS Gold standard Bioconcentration database QSAR Awareness Day, JRC, Ispra,Italy

  3. 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 QSAR Awareness Day, JRC, Ispra,Italy

  4. 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 Kithttp://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. QSAR Awareness Day, JRC, Ispra,Italy

  5. IT strategy • Desktop installation: MySQL database and standalone application (AmbitDatabaseTools) on the same PC • Intranet installation: MySQL database on a server and standalone application (AmbitDatabaseTools) on the user PCs • Internet installation – My SQL Database and web server (JSP and Servlets), Web browser as user interface QSAR Awareness Day, JRC, Ispra,Italy

  6. Ambit overview • The AMBIT database: • storeschemical 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 system’s great strengths is that any dataset can be imported for comparison and analysis. AMBITDatabaseTools 1.21 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. • ECB QMRF inventory – a tailored version of Ambit database (under development). Will store information in QMRF. Large effort on standardization QSAR Awareness Day, JRC, Ispra,Italy

  7. AMBIT Database Today Not restricted to these datasets! Any dataset can be imported. (e.g. DSSTox, AQUIRE, LLNA …) QSAR Awareness Day, JRC, Ispra,Italy

  8. AMBIT Database Schema QSAR Awareness Day, JRC, Ispra,Italy

  9. AMBIT Online: Similarity search QSAR Awareness Day, JRC, Ispra,Italy

  10. AMBIT Online:Query result QSAR Awareness Day, JRC, Ispra,Italy

  11. Links to other databases: example: KEGG QSAR Awareness Day, JRC, Ispra,Italy

  12. Information about QSAR models QSAR Awareness Day, JRC, Ispra,Italy

  13. Search AQUIRE database online QSAR Awareness Day, JRC, Ispra,Italy

  14. Search EURAS Bioconcentration database online QSAR Awareness Day, JRC, Ispra,Italy

  15. Ambit Database Tools 1.21 Standalone application available at http://ambit.acad.bg/downloads • AMBITDatabase main window consists of following areas: • Task bar on the left; • Molecule browser (top right); • Molecule data tabs (bottom right); • Fast SMILES entry panel (top); • Status bar at the bottom. QSAR Awareness Day, JRC, Ispra,Italy

  16. Demo: • Finding basic information about a query compound in the database • Complex query in the database –retrieve data meeting multiple criteria from Ambit database • Import data from EURAS Gold standard Bioconcentration database QSAR Awareness Day, JRC, Ispra,Italy

  17. Exercise 1. Finding basic information about a query compound in the database • Launch AmbitDatabaseTools 1.20 • Start menu/ All Programs/ CEFIC-LRI/Ambit 1.20 Ambit database tools main screen. Various tasks can be started from the menu options at the left panel. This exercise uses Search / CAS RN menu to lookup for compound with specific CAS RN QSAR Awareness Day, JRC, Ispra,Italy

  18. Exercise 1a. Lookup by CAS RN • An input box appears • Enter 66-25-1 and click OK. • The result appears in top panel (Molecule browser) • Click on 3D tab to view the 3D structure • Further processing – save, calculate descriptors, etc. QSAR Awareness Day, JRC, Ispra,Italy

  19. Exercise 1b. Retrieve descriptors • The objective of this exercise is to retrieve values of several descriptors from the database. The descriptors we are interested are • LogP • Crossectional diameter • Maximum diameter • Molecular weight • Use Molecule/Advanced data retrieval menu QSAR Awareness Day, JRC, Ispra,Italy

  20. Exercise 1b. Retrieve descriptors • The following window appears • Check Read descriptors row • The following window appears: • Check following descriptors : • XLogPDescriptor • WeightDescriptor • CrossectionalDiameterDescriptor • MaximumDiameterDescriptor QSAR Awareness Day, JRC, Ispra,Italy

  21. Exercise 1b. Retrieve descriptors • The results appear in Descriptors tab • Further processing – save, etc. QSAR Awareness Day, JRC, Ispra,Italy

  22. Exercise 1c. Retrieve AQUIRE data • Use Molecule/AQUIRE menu to retrieve toxicity data for hexaldehyde • The results can be observed in bottom panel, EXPERIMENTAL data tab. Click on each row to view more details. • Save to a file using File/Savemenu (sdf, csv, xls, txt) QSAR Awareness Day, JRC, Ispra,Italy

  23. SDF file for hexaldehyde • CDK 6/23/07,13:23 19 18 0 0 0 0 0 0 0 0999 V2000 -0.0187 1.5258 0.0104 C 0 0 0 0 0 0 0 0 0 0 0 0 • 0.0021 -0.0041 0.0020 C 0 0 0 0 0 0 0 0 0 0 0 0 • 1.4167 2.0553 -0.0004 C 0 0 0 0 0 0 0 0 0 0 0 0 • -1.4333 -0.5336 0.0129 C 0 0 0 0 0 0 0 0 0 0 0 0 • 1.3963 3.5622 0.0079 C 0 0 0 0 0 0 0 0 0 0 0 0 • ……… • 6 18 1 0 0 0 0 • 6 19 1 0 0 0 0 • M END • > <NSC> • 2596 • > <CrossSectionalDiameterDescriptor [Angstrom]> • 2.4897 • > <XLogPDescriptor> • 1.7530 • > <MaximumDiameterDescriptor [Angstrom]> • 8.1759 • > <SMILES> • O=CCCCCC • > <AQUIRE> • LC50=22000,ug/L Pimephales promelas • LC50=22000,ug/L Pimephales promelas • > <CasRN> • 66-25-1 • > <WeightDescriptor> • 100.0888 QSAR Awareness Day, JRC, Ispra,Italy

  24. XLS file for hexaldehyde QSAR Awareness Day, JRC, Ispra,Italy

  25. Exercise 2.Complex queries: Use Ambit database to retrieve data that meet multiple criteria • UseSearch options /optionsmenu to configure desired searches • Switch to Similarity tab and set 0,7 for Tanimoto threshold (we will be searching for structures with Tanimoto similarity > 0.7) QSAR Awareness Day, JRC, Ispra,Italy

  26. Exercise 2a.Similarity search • UseSearch/Structure searchmenu to invoke advanced query window • Draw dimetylphtalate as shown at the figure • Click Similarity button • Browse the 7 compounds found (in Molecule Browser) • Go to Search/options and lower threshold to 0.6 • Use Search/Structure search/Similarity again with the same compound QSAR Awareness Day, JRC, Ispra,Italy

  27. Exercise 2a.Similarity search • Now there are 156 compounds with Tanimoto similarity > 0.6 • We will be using Molecule/Save as datasetmenu to store the query results into the database • Hint: you can store query results directly into database, without loading into Molecule Browser, by setting Search Options/Result destination – DATABASE and then performing the query QSAR Awareness Day, JRC, Ispra,Italy

  28. There can be many Ambit databases running on one MySQL server Within Ambit database the chemical compounds can be grouped in many subsets. Typically, one database consists of multiple subsets (datasets), corresponding to the origin of the data (e.g. the file used to import the compounds) The search results can be marked as a separate subset within Ambit database The search can be performed within entire Ambit database or just on a selected subset. This allows to use results of one query as a input to another and restrict the set of structures step by step Database server (MySQL) Ambit Database 1 (e.g. ambit) Dataset 1 (200 000 structures from NCI) Dataset 2 (600 structures from DSSTox EPA Fathead Minnow) Dataset 3 (AQUIRE) Dataset 4 (DSSTox carcinogenic potency data) Dataset 5 (EURAS Bioconcentration factor data) Dataset 6 (my similarity search results) Ambit Database 2 (e.g. test_database) … Ambit Database N (e.g. my_secret_dataset) Other (non-Ambit) databases Database and datasets - background QSAR Awareness Day, JRC, Ispra,Italy

  29. Exercise 2a.Similarity search • Use Molecule/Save as datasetmenu to store the query results into the database • In the dialog box (as at right), add “+”button to add a new entry for the dataset. • Type in the name for the dataset (e.g. “Similarity search Tanimoto > 0.6”) • Click OK QSAR Awareness Day, JRC, Ispra,Italy

  30. Exercise 2a.Similarity search • Now the new dataset is available in the datasets list and can be used to restrict subsequent queries • Use Search options/Dataset menu to select which dataset to be searched, select “Similarity search Tanimoto > 0.6” and click OK Note: this will not load any structures into Molecule browser! QSAR Awareness Day, JRC, Ispra,Italy

  31. Exercise 2b.Pre-set physicochemical profile • The objective is to extract compounds that have physicochemical properties, relevant for bioaccumulation from the set of structurally similar compounds found by previous query. • The recommended descriptors and ranges are: • LogP < 4.5 • Molecular weight < 1100 • Cross sectional diameter < 17.4 Å • Maximum diameter < 43 Å QSAR Awareness Day, JRC, Ispra,Italy

  32. Exercise 2b.Pre-set physicochemical profile • Use Search/Structure search menu • The window with options for structure, descriptors and experimental data queries appears. • Click on Descriptorsicon to obtain a list of descriptors available in the database QSAR Awareness Day, JRC, Ispra,Italy

  33. Exercise 2b.Pre-set physicochemical profile • Select XLogP descriptor (click on first column • Click on Condition column and select “<” sign. • Double click on the next column and enter 4.5 • Repeat with descriptors: • WeightDescriptor (Molecular weight) < 1100 • CrosssectionalDiameterDescriptor (crossectional diameter) < 17.4 • MaximumDiameterDescriptor (maximum diameter or maximum length) < 43 • Click the Search button QSAR Awareness Day, JRC, Ispra,Italy

  34. Exercise 2b.Pre-set physicochemical profile • 123 out of the 156 structurally similar compounds have the predefined profile. • The descriptor values can be inspected in the Descriptors tab QSAR Awareness Day, JRC, Ispra,Italy

  35. Exercise 2c.Retrieve available toxicity data • Use Search Options/Options menu to select he endpoint • Select AQUIRE tab • Select LC50 (Lethal concentration to 50% of test compounds) from the first list box QSAR Awareness Day, JRC, Ispra,Italy

  36. Exercise 2c.Retrieve available toxicity data • The next step is to tell the software we want to retrieve the data for all retrieved compounds (not only for the current structure). To do this: • Select Molecule processing tab • Select Molecule Browser: Current set of structures from the first list box QSAR Awareness Day, JRC, Ispra,Italy

  37. Exercise 2c.Retrieve available toxicity data • Use Molecule/AQUIRE menu to retrieve LC50 data for the current set of compounds • Click Start button. QSAR Awareness Day, JRC, Ispra,Italy

  38. Exercise 2c.Retrieve available toxicity data • Browse the compounds to view AQUIRE data at the bottom panel • Repeat the same procedure to retrieve BCF data from AQUIRE QSAR Awareness Day, JRC, Ispra,Italy

  39. Exercise 2d.Retrieve available toxicity data (ER Binding) • Structure/Search menu • Click experiments • Select DSSTox-ERBinding • Select Endpoint=“ER RBA” • Click Search QSAR Awareness Day, JRC, Ispra,Italy

  40. Exercise 2d.Retrieve available toxicity data (ER Binding) • Browse ER Binding data, save results into file QSAR Awareness Day, JRC, Ispra,Italy

  41. More exercises • Batch search • Import structures into database • Import descriptors and experimental data (e.g. bioconcentration factor dataset) • Import QSAR models • Database processing • Descriptor calculation • Atom environments, Fingerprint, SMILES generation • Create new (empty) database. • Create users for the new database • Import compounds QSAR Awareness Day, JRC, Ispra,Italy

  42. Ambit - Summary • AMBIT software is a set of libraries and tools, providing various chemoinformatics 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. QSAR Awareness Day, JRC, Ispra,Italy

  43. Thank you! Questions?

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