jchem base chemical database

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Szilárd Dóránt

May, 2005

JChem Base chemical database

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Jchem Base chemical database — May 2005

Contents

Introduction

Structural overviewCompatibilityAdministrationJChem tablesFingerprintsStructural search

Structure cache

StandardizationSearch optionsJSP exampleAPI examplesPerformanceFuture plans

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Introduction

JChem Base provides high performance Java based tools for the storage, search and retrieval of chemical structures and associated data.

These components can be integrated into web-based or standalone applications in association with other ChemAxon tools.

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Structural overview

RDBMS (e.g. Oracle, MySQL, etc.) : Storage and security

JDBC driver: Standard interface to the RDBMS

JChem Base API:

•Chemical logic

•Structure cache

Application Web application (JSP)

Web

browser

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Compatibility and integration

File formats:• SMILES• MDL molfile (v2000 and v3000)• MDL SDF• RXN• RDF• MRV

Integration:• 100% Java • extensive API• JChem Cartridge for Oracle

Database engines:• Oracle• MySQL• MS SQL Server• PostgreSQL• MS Access• DB2• etc.

Operating systems:• Windows• Linux• Mac OS X• Solaris• etc.

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Administration with JChemManager

User interface for• creating tables• import• export• deleting rows• dropping tables

Most functions are also available from command-line.

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The property table

The property table stores information about JChem structure tables, including:

• Fingerprint parameters• Custom standardization rules• Recent changes (to optimize cache updates)• Other table options and information• Database-related licence keys

More than one property table can be used, each property table represents a particular JChem environment.

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The structure of JChem tables

Column name Explanation

cd_id unique numeric identifier in the table

cd_structure the imported structure in the original format, without modifications (except for the removal of data fields)

cd_smiles the standardized structure in ChemAxon Extended Smiles (cxsmiles) format, used by the search process

cd_formula the formula of the standardized structure

cd_molweight the molecular weight of the standardized structure

cd_hash hash code used for duplicate filtering (PERFECT search)

cd_flags can store row specific option, e.g. overriding the chiral flag

cd_timestamp the date and time of the insertion of the row

cd_fp… fingerprint columns

[user fields] custom data fields can be added by the user

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• Chemical Hashed Fingerprints encode structural patterns in bit strings

• If structure A is a substructure of structure B, every bit in B’s fingerprint will be set that is set in structure A’s fingerprint:

• Tanimoto similarity of hashed fingerprints can be used for diversity analysis and similarity search:

Chemical Hashed Fingerprints

YXYX

YXYX

&BitCountBitCountBitCount

&BitCount,Tsim

AB&A

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Structural search in database

Two stage method provides optimal performance:

1. Rapid pre-screening reduces the number ofpossible hit candidates

- Chemical Hashed Fingerprints are used forsubstructure and superstructure searches

- Hash code is used for duplicate filtering(usually during compound registration)

2. Graph search algorithm is used to determine the final hit list

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Structure Cache

• Contains Fingerprints for screening and ChemAxon Extended SMILES for ABAS

• Instant access to the structures for the search process

• Reduced load on the database server

• Incremental update ensures minimum overhead after changes in the table

• Small memory footprint due to – SMILES compression– Optimized storage technique

• Approximately 100MB memory needed for 1 million typical drug-like structures (using 512 bit long fingerprints)

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Standardization

• Default standardization includes:

– Hydrogen removal

– Aromatization

• Custom standardization can be specified for each table by specifying an XML configuration file at table creation or in the “Regenerate” dialog of JChem Manager (jcman)

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Custom Standardization Example

afterbefore

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Database search options

• Maximum search time / number of hits • SQL SELECT statement for pre-filtering• Ordering of results• Result table• Inverse hit list • Chemical Terms filter constraint

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JSP example application

• Open source, customizable

• Features:

– Substructure, Superstructure, Exact and Similarity search

– Molecular Descriptor similarity search with descriptor coloring

– Substructure hit alignment and coloring, inverse hit list

– Chemical Terms filter

– Import / Export

– Export of hits

– Insert / Modify / Delete structures

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API example : connecting to a database

ConnectionHandler ch = new chemaxon.jchem.db.ConnectionHandler(); ch.setDriver(“oracle.jdbc.driver.OracleDriver”);ch.setUrl(“jdbc:oracle:thin:@localhost:1521:mydb”);ch.setPropertyTable(“JChemProperties”);ch.setLoginName(“scott”);ch.setPassword("tiger");ch.connect();// the java.sql.Connection object is available if needed:Connection con=ch.getConnection();…// closing the connection:ch.close();

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API example : database import

Importer importer = new chemaxon.jchem.db.Importer();importer.setConnectionHandler(conh);importer.setInput(“sample.sdf”);// importer.setInput(is); // alternatively a stream can also be specifiedimporter.setTableName(“SCOTT.STRUCTURES”); importer.setHaltOnError(false);importer.setDuplicateImportAllowed(false); //can filter duplicates

// specifying SDFile field - table field pairs:String fieldPairs = “DB_Field1=SDF_Field1; DB_Field2=SDF_Field2”;importer.setFieldConnections(fieldPairs);int importedCount = importer.importMols();System.out.println( “Imported” + importedCount + “structures” );

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API example : database export

Exporter exporter = new chemaxon.jchem.db.Exporter();exporter.setConnectionHandler(conh);

exporter.setTableName(“structures”); //data fields to be exported with the structure:exporter.setFieldList(“cd_id cd_formula name comments”);String fileName=“output.sdf”;OutputStream os=new FileOutputStream(fileName);exporter.setOutputStream(os);exporter.setFormat(“sdf”); int exportedCount = exporter.writeAll();System.out.println(“Exported ” + exportedCount + “structures”);

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API example : database search

JChemSearch searcher = new chemaxon.jchem.db.JChemSearch();searcher.setConnectionHandler(ch);searcher.setSearchType(JChemSearch.SUBSTRUCTURE)searcher.setQueryStructure(“c1ccccc1”);searcher.setStructureTable(“SCOTT.STRUCTURES”);// a query that returns cd_id values can be used for prefiltering:Searcher.setFilterQuery(

“SELECT cd_id FROM structures, biodata WHERE ”+ “structures.cd_id = biodata.cd_id AND biodata.toxicity < 0.3” );

searcher.setWaitingForResult(true); // otherwise runs in a separate threadsearcher.setStructureCaching(true); // caching speeds up the searchsearcher.run();// getting the results as cd_id values:int[] results=searcher.getResults();

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API example : inserting a structure

// ConnectionHandler, mode, table name and data field names:UpdateHandler uh = new chemaxon.jchem.db.UpdateHandler(

ch, UpdateHandler.INSERT, “structures”, “comment, stock”);uh.setValueForFixColumns(“c1ccccc1”); // the structure// specifying data field values:uh.setStructureValueForAdditionalColumn(1, “some text”); uh.setStructureValueForAdditionalColumn(2, new Double(8.5));uh.setDuplicateFiltering(true); // filtering duplicate structuresint id=uh.execute(true); // getting back the cd_id of the inserted structureif ( id > 0 ) { System.out.println(“Inserted, cd_id value : ” + id);} else { System.out.println(“Already exists with cd_id value : ” + (-id));}// storing update information, the database connection remains open : uh.close();

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Performance (1)

Compound registration:

Substructure search in a table of 3 million compounds:

Server parameters: Windows XP; 1 CPU: Intel P4 3.0GHz; 2GB RAM; Oracle 9i

12min 26s8min 17s200,000

6min 20s4min 11s100,000

45s32s10,000

Duplicates checkedDuplicates not checked

Elapsed timeNumber of compounds

10.749740

1.20

0.9936

0.112

Search time (s)Number of hitsQuery

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Performance (2)

Similarity search:Tanimoto >0.8

Server parameters: Windows XP; 1 CPU: Intel P4 3.0GHz; 2GB RAM; Oracle 9i

1.3336

1.3156

1.524

Search time (s)Number of hitsQuery

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Future plans

• Additional layer: JChem Server (later also as grid)

• Structural keys as optional extension to current fingerprints

• Tables for storing query structures

• Tables for storing general (Markush) structures

• Partial clean option for hit alignment

• Installer

• etc.

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Summary

ChemAxon’s JChem Base toolkit provides sophisticated methods to deal with chemical structures and associated data.

The usage of fingerprints and structure cache provide high search performance.

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Links

• JChem home page:– www.jchem.com

• Live demos:– www.jchem.com/examples

• API documentation:– www.jchem.com/doc/api

• Brochure:– www.chemaxon.com/brochures/JChemBase.pdf

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Máramaros köz 3/a Budapest, 1037Hungary

[email protected]

www.chemaxon.com

Thank you for your attention

jchem base chemical database

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