A large-scale chemical data integration system Gaia Paolini Pfizer - PowerPoint PPT Presentation

A large-scale chemical data integration system Gaia Paolini Pfizer Confidential 1

Large-Scale Chemical Data Integration Summary � Current situation � Business case � Aims � The design process � Functionality � Applications

Large-Scale Chemical Data Integration The Project � A large chemical data warehouse to store and integrate Pfizer and third-party information using chemical structure as the natural entry point � Millions of chemical structures � Based on the DayCart Oracle Cartridge

Large-Scale Chemical Data Integration Why Integrate? � The need to integrate and mine disparate sources of data Mergers & acquisitions In-licensing In-house data 3 rd -party databases

Large-Scale Chemical Data Integration Why Integrate? � Data available to buy and integrate from external sources � Need for active chemoinformatics research repository � Opportunity to highlight connections � Chemical Properties � Structural similarities

Large-Scale Chemical Data Integration Aims of the Data Warehouse � Enable chemical/pharmaceutical data mining and knowledge discovery � Store chemical structures and properties together with related entities � Biology � Portfolio � Inventory

Large-Scale Chemical Data Integration Scope � Data warehouse � Common consolidated set of data � Repository of selected fields from Pfizer and third-party data � Source independent � Chemo-centric : indexed on structure not compound ID � Emphasis on data integration rather than front end client application

Large-Scale Chemical Data Integration Requirements � Unique chemical structure indexing � Multiple and hierarchical tautomeric and stereochemical indexing � Integrate internal and external data � Indexed by chemical structure � Integrate chemo- and bio-informatics communities � Fit-for-purpose model architecture � Uses corporate dictionaries to standardise entities � Create connections and synonym tables

Large-Scale Chemical Data Integration What do we want from our data? � Data should be easy to � access � compare phase � exchange launched � manipulate target compound

Large-Scale Chemical Data Integration Why data integration?

Large-Scale Chemical Data Integration Database Design Decisions � Central data warehouse � Selective data integration � Focus on chemical structure � SMILES representation in DayCart � Flexible compound wiring

Large-Scale Chemical Data Integration Central Data Warehouse � Data is decoded, loaded, cleaned and mapped Pfizer ETL DataMart Chemical Structure Integration Staging DrugStore External DataMart Tables warehouse Chemical DataMart External structure Structures integration

Large-Scale Chemical Data Integration Selective data integration Database Drug Store Pipeline Pilot Spotfire Flexible UI Ad-hoc queries and data mining Pfizer marts … 3 rd -party … Contributed research…

Large-Scale Chemical Data Integration Data Integration � Consolidated, homogeneous set of data: � One index for every entity � One unit of measure for every property � We can: � Highlight connections between entities � Create new connections � Filter on properties � Interface to other databases

Large-Scale Chemical Data Integration Chemo-centric design � Every entity and property is connected to a chemical structure � Seamless integration of different data sources � Can measure how a data source enriches chemical space � Consistent modelling of tautomers and stereo- isomers � Easy to apply hierarchical order (e.g. parent-child) � Any (and multiple) grouping of structures allowed � Intuitive application of chemo-informatics methods

Large-Scale Chemical Data Integration DayCart Oracle Cartridge � SMILES chemical representation � Structure comparison, transformation, manipulation � Fast data retrieval

Large-Scale Chemical Data Integration DayCart: Chemical Representation � SMILES syntax support � Compact, linear representation � Self contained language � Computer friendly & searchable � No proprietary data types!

Large-Scale Chemical Data Integration DayCart: Functions for Chemical Information � Exact match � Substructure � Similarity � Tautomers � Salts � Stereochemistry

Large-Scale Chemical Data Integration DayCart: Indexes � Four (domain) indexes � DDBLOB: substructure, similarity � DDGRAPH: tautomers, stereochemistry � DDROLE: salts � DDEXACT: exact match � Essential for performance � Trade-off data-load/index building � Partitioning? (Next version)

Large-Scale Chemical Data Integration DayCart: Indexes DDBLOB DDGRAPH DDROLE 700 600 500 Time (in mins) 400 300 200 100 0 1,000,000 2,000,000 3,000,000 4,000,000 5,000,000 No of Records being indexed

Large-Scale Chemical Data Integration DayCart: VCS_normalize � Transform structures according to database rules encoded in SMIRKS � Apply internal business rules � Standardize structures � Performance?

Large-Scale Chemical Data Integration Applications � Perform large-scale data mining � Accelerate exploration of new ideas at project inception � Repository for chemo-informatics knowledge � Advanced research database for computational chemists

Large-Scale Chemical Data Integration Example Query: chemical toolbox Find all screens and compounds tested against each target Filter target Find all activity results & rank compounds compound Filter out non druggable compounds Select available compounds Filter out non-selective compounds activity Select top ten representative diverse structures “Show me the most potent, selective tools for each target, available in- house”

Large-Scale Chemical Data Integration Acknowledgements

Large-Scale Chemical Data Integration Thank you!