1. Misha Kapushesky http://www.ebi.ac.uk/expressionprofiler November 28, 2003 Expression Profiler: Next Generation

2. MIAMExpress –MIAME-compliant microarray data submission tool ArrayExpress –Public repository for microarray data, aimed at storing well-annotated data in accordance with MGED recommendations Expression Profiler –Microarray exploratory data analysis and management platform Background

3. ArrayExpress Other Microarray databases www EBI Expression Profiler External Bioinformatics databases Data analysis www Queries www MIAMExpress MAGE-ML Submissions Array Manufacturers LIMS Microarray software Data Analysis software MAGE-ML import, export Local MIAMExpress Installations Data pipelines MAGE-ML Overall Infrastructure

4. DesignElements (spots, genes) ArrayExpress Data Representation spots measurements BioAssays (hybridizations, data transformations) QuantitationTypes (signal intensity, ratio etc.) in MAGE/ArrayExpressin Expression Profiler

5. ArrayExpress: Expression Data Matrices BioAssays (hybridizations, data transformations) QuantitationTypes (signal intensity, ratio etc.) BioAssayData1 BioAssayData2 select QuantitationTypes select BioAssays DesignElements (QT,BA) pairs DesignElements (spots)

6. EP:NG – Design Goals Maintain present functionality Create an extensible framework Distinct functional components Uniform look-and-feel Flexible collaborative environment

7. EP:NG Framework How it works… –RDBMS-driven (users, interface, metadata) –Component-based web app platform –XML/XSLT HTML rendering –Available as Web Service Written in… –XML/XSLT – transformations, component chaining –PERL -- for inter-component glue –C, C++, R, etc. -- integrated 3 rd party algorithms

8. ArrayExpressR (S-SPLUS) EP Filesystem Architecture Overview XML component descriptions Chainable, extensible components

9. SECTIONS Inputs Grouped into subsections Input names, type, validation type Used for rendering Dynamic data External service access EP DB/file system access, etc. Outputs Output name, type, validation type Output format (e.g. regular expression) ACTION URL (or other definition) EPC target IDs EPC XML Components

10. Transformed with XSL Accessing EP DB for definition of dynamic input elements

11. Available Components Data Selection Data Transformation –Raw intensities Log 2 (ratio) –Average row identifiers –Missing value imputation: via KNNimpute* –Data transposing Hierarchical Clustering + K-groups Clustering Clustering Comparison: via R** Ordination (COA, PCA): via R (ade4)*** Between Group Analysis: via R (ade4)**** *Troyanskaya et al. Bioinformatics. 2001 Jun;17(6):520-5 **Developed in our group (Aurora Torrente) ***Ade-4: http://pbil.univ-lyon1.fr/ADE-4 ****Culhane et al., Bioinformatics. 2002 Dec;18(12):1600-8

12. Components Coming Soon Two-way clustering Iterative Signature Algorithm (Naama Barkai, Jan Ihmels) Gene ordering (Karlis Freivalds) Bioconductor integration (UCL) Normalization methods –LOWESS,... Statistical analysis methods –ANOVA, SAM,... More! (contributors?) EP:NG is an open source project – if you are interested in contributing, testing or just discussing ideas, let us know!

13. EP:NG Platform Features User + data management –Multiple folders, data sharing, collaborative features Analysis History –Analysis steps export/re-application Visualization Framework –Interactivity: gene searching, cluster/gene group selection + tagging, zooming, etc. EP:NG is an open source project – if you are interested in contributing, testing or just discussing ideas, let us know!

14. Original EP Development: Jaak Vilo (Tartu) Patrick Kemmeren (Utrecht) Misha Kapushesky EP:NG Framework Development: Patrick Kemmeren (Utrecht) Misha Kapushesky Visualization Components (under development): Steffen Durinck (Leuven) Clustering Comparison: Aurora Torrente Christine Körner (Leipzig) PCA/COA/BGA: Aedín Culhane (Cork) Gene Ordering: Karlis Freivalds (Riga) Normalization (under development): Tom Bogaert (Leuven) Discussions: EBI Microarray Informatics Team Contributors from the open source community EP:NG is an open source project – if you are interested in contributing, testing or just discussing ideas, let us know! Acknowledgements