Iconix Extensible Informatics System (IXIS™)

Category Cross-Omics>Biomarker Discovery/Tools

Abstract The Iconix Extensible Informatics System (IXIS) is a multi-dimensional data capture, analysis, visualization and reporting software system initially developed to support DrugMatrix®, one of the world’s largest toxicogenomics database of microarray and pharmacology data.

The software can be licensed and customized for use with any proprietary multi-dimensional datasets.

The base system is scalable and flexible, built on a technology base that includes an Oracle database schema, a BEA Weblogic® Java™ application server and a Tibco General Interface™ user interface.

IXIS supports the needs of toxicologists, pharmacologists, chemists and drug discovery scientists.

Additional data types, such as proteomics and metabonomics, can easily be added to support all aspects of pharmaceutical R&D.

IXIS software is capable of handling multiple types of data. In its current version, the software integrates data from the following domains: gene expression, histopathology, clinical chemistry, molecular pharmacology, literature, pathways, and compound structures.

In addition, IXIS software incorporates analytical and statistical tools that take advantage of the integrated nature of the dataset, allowing the construction of sophisticated queries across the information, and the analysis of data in all information domains.

Finally, the IXIS Software interfaces with external data analysis tools such as Spotfire, and the MDL ISIS molecular structure database system, as well as providing an open, documented database that can be accessed from any software that can connect to Oracle.

Example Features --

Hierarchical Clustering - The many integrated information domains in IXIS enable the analysis of diverse types of data using common analytical methods.

Gene expression data are hierarchically clustered and displayed in a gene expression matrix heat map.

Similar analyses can be performed on clinical chemistry, hematology, molecular pharmacology, and 'Drug Signature biomarker' sets.

This diverse set of tools allows one to 'identify patterns' and relationships Not easily discerned in other systems.

Pathway Impact - By integrating 'biological pathway' information with 'gene expression' data, IXIS supports global visualization of the impact of compound treatment effects on ‘gene expression’ in affected pathways.

Researchers can quickly identify pathways relevant to both efficacy and safety.

Pathway Response Chart - The IXIS system is optimized to identify trends within the global dataset.

By integrating with standard visualization tools such as Spotfire, IXIS can display a ranking of all experiments relative each other, based on the 'transcriptional response' of component genes.

Experiments of interest can be identified within the trend.

Fully Customizable Features --

Simple Search - Search for any item by name, and synonyms, symbols and identifiers are automatically included.

Example: find drug “Lipitor” retrieves “Atorvastatin”. Search can be configured to include multiple namespaces in the database simply by adding metadata.

Advanced Query - Search for any item based on one or more annotations or properties. Supports filtering and multiple “and” logic. In combination with the list manipulation tools, any complex logic can be executed.

Example: find drugs that inhibit HMG CoA Reductase with an IC50 less than 10 nM AND that induce transcription of genes in the Cholesterol Biosynthesis pathway greater than 2-fold.

Flexible dynamic query builder can be extended to new data types by editing Extensible Markup Language (XML) in the graphical user interface (GUI) code-base.

A toolbox with hundreds of specific queries is available, from which an infinite number of combinations can be built.

Workspaces and Lists - Search results are saved in private user workspaces. Results can be displayed, edited and imported into analytical tools.

The user workspaces and lists are stored on the server, allowing transparent use from any computer. Workspaces are administered by each user through a GUI.

List Combinations - Lists can be combined using Union, Intersect and Subtract tools. These, in combination with the 'Advanced Query' tool, allow an infinite number of logical queries to be built in the GUI.

Example: find genes that are induced by Clofibrate that are Not induced by Fenofibrate. List management is built into the base system.

mport/Export - Lists of interesting results can be e-mailed to colleagues, who can import the list into their own workspaces for review.

Example: a publication reports a 10-gene biomarker for hepatotoxicity. A text file with the probe set names for all 10 genes can be imported into an IXIS list and sent for review.

Queries can be run to search the database for similar patterns. Import/Export is built into the base system.

Browsing Data - With one click, a web-based interface presents all information related to an item identified in search results.

Example: Viewing the gene for HMG CoA Reductase, a scientist can access all of the associated names and symbols, Gene Ontology (GO) terms, experimental conditions that induce and repress that gene, other genes that are co-regulated, pathways containing the gene and drugs designed to interact with the gene product.

The base system supports 8 data dimensions: gene, compound, assay (clinical and pharmacological), expression experiment, expression study, signature, histopathology and pathway.

The data model and user interface can be easily extended to add new dimensions, e.g., proteomics.

Scalability - The IXIS platform has been used with databases of over 50 million records with good interactive performance.

A dataset of 50M records requires about 100GB of Oracle disk space and 2GB of application server Random Access Memory (RAM). Increasing the dataset size increases the system requirements in a linear relationship.

System Requirements

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Manufacturer

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G6G Abstract Number 20286

G6G Manufacturer Number 100879