Data systems supporting chemical informatics and small molecule discovery for crop protection research.

Transcription

1 Data systems supporting chemical informatics and small molecule discovery for crop protection research. Mark Forster - Oracle Life Science User Group Meeting. April 2006.

2 Presentation Outline. Syngenta business domains, history and legacy systems Data model for chemical substances, samples, vessels and experimental data. An integrated system for crop protection research - Components and technologies. Validating molecular structures. Distributed molecular property calculations

3 Business model, history and legacy systems. Syngenta formed 2001 merger of Zeneca and Novartis agribusiness units. Main business domains Crop Protection: Herbicides, Insecticides, Fungicides Plant Biotechnology: New traits, marker assisted breeding Flowers and Vegetables: Seeds / Treatments. Ex Novartis Legacy System Daylight toolset. Ex Zeneca Legacy System MDL Isis/Host based. Syngenta Integrated System - Active Ingredient Research Information Management (AIRIM) Accelrys based.

4 Crop Protection AI discovery Not the Pharmaceutical discovery model. Bulk of initial hits based in-vivo / in-vitro screening of 1000s of compounds. Compound screening pipeline filling Combinatorial chemistry Compound purchasing In house custom synthesis Structure based rational design - Only possible where target known and structure available Fewer projects.

5 Data model Substance - Abstract or conceptual molecule. - Typically defined by structure drawing, stereo flag, comment. Sample - Physical instantiation of one substances, or a mixture of substances. - Sample can be of unknown structure(s) but can still be screened. Vessel - Tube, Plate or bottle holding physical sample. - Have bar codes and changing location as they move through process. Experiment - A test carried out with a sample, yields result(s) of various types.

6 System Components CODA LVIS BITS Corporate compound database. Logistics / Vessel Information system. Biology IT data system. QUART Querying and reporting Tool. SOLSTICE Web based framework for molecular property calculation and database searching.

7 High level system architecture Formulation & liquid handling robots PDA Data Capture Solstice Web App.Net clients Other DBs Genomic data.net middle tier Oracle 9i Win 2000 Apache Perl / Java SGI / Linux Farm Chemical Structure DB (CODA/Accord) Vessel Logistics (LVIS) Biology Screening Data (BITS) Quart / Cognos ReportNet

8 System Architecture Issues Distinct Schema even for one physical database - Middle tier control of database access. - Compensation Logic.Net 1.0 Early adoption, Immature, 32 bit code, memory limited App server stability. Remote method calls Desktop application deployment (packaging)

9 Chemical data cartridge and compound registration. Accord 6 Chemistry Engine SDK Store, index, search molecular structure and reactions. Search exact structure, substructure, similarity. Access via SQL, PL/SQL, or ODBC, JDBC language libraries. Additional CODA tables Syngenta specific data, eg registration information. Structure visualisation Accord chemistry control, Excel client [Accord web kit for JSPs and web viewer (Applet)]

10 Validating molecular structures. Accelrys structure checker. Ensures consistent form for molecular structure(s). Enforces user specified rules for structure diagrams. Changes group molecular structure to meet rules if possible. Java Component, accessed by command line or SOAP. Example 1 (Nitrobenzene) Example 2 Input Output 5 Valent N Charge separated group form Input Output Pyridinone Hydroxypyridine

11 Solstice capabilities. Simple web interface Upload molecule sets Typically MOL,SDF,SMILES files, store for later reuse. Extensive set of molecular property calculations Primarily applied to small molecules. Eg logp, H donor/acceptor, Esolv, Search large compound databases Eg Vendor database of several millions structures. Option for sophisticated graphical displays.

12 Solstice Web based molecular calculation framework. Solstice has simple origins. How to provide a simple web interface to useful chemical (command line) calculations. Typically on Silicon Graphics Solstice 1 and 2 based on the Apache Web server. Perl code embedded in HTML (Mason). Solstice 3.0 is a major upgrade to the Chemistry Design tools Web interface. The new release employs a Service Oriented Architecture (SOA) approach.

13 Service Oriented Architecture Functionality provided by language and operating system independent Services. Data transfer achieved via XML documents. Promotes interoperability between heterogeneous operating systems and programming languages.

14 Previous Solstice (2.x) Architecture Included Apache Web Server Mod Perl and Mason File based data persistence Network Queuing System (NQS)

15 New tools for Solstice 3.0 J2EE Application Server SOAP (Service Oriented Architecture Protocol) Data transport Data persistence Job Submission Framework JBoss Is the glue that holds all of the J2EE components together. Apache Axis Is the toolkit which provides the SOAP implementation. Apache XML Beans XML-Java data binding. Provides extensive API to navigate XML Schema. Oracle & Hibernate Object Relational data bridge for Java. Sun Grid Engine Grid computing framework to support distributed processing of Solstice jobs.

16 Solstice 3 - The ntier view Solstice Client Façade Application Resource Web Browser, Excel Worksheet, Java Applet HTTP Web Application Database HTTP HTTP EJB and MBeans Compute Web Services RMI Data files JMS External app eg CombiChem

17 Sun Grid Engine Configuration SGI Head Node Execution nodes SGI1 SGI2 Solstice Master Local Disk Control job on Solstice Master copies data to/from the shared disk on the SGE head node. Jobs are executed remotely and the data is copied back. Shared Disk Linux Head Node Shared Disk Execution nodes 42 x 2 CPU IBM Xeon Blades - Centos Linux

18 Retrieving chemical / biological data Cognos ReportNet. Business metalayer for simplified reporting interface. Accord for Excel Enterprise. Data retreival and several calculation types. Visualisation tools Accelrys Chemistry (Active-X) Control JME (2D) applet JMOL (3D) applet Cross platform, high performance, free. AVS Vis Elements, Particles

19 Acknowlegements Graham Mullier, Jim Harrison, Steve Higgins AIRIM team