Agilent Genomics Software Future Directions

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Agilent Genomics Software Future Directions Michael Rosenberg, PhD Director, Genomics Software

Agilent: A Focused Measurement Company Serving Diverse End Markets Electronic Measurement 2008 Revenue: $3.6 Billion Bio-Analytical Measurement 2008 Revenue: $2.2 Billion General Purpose 37% Communications 25% Chemical Analysis 20% Life Sciences 18% Other General Industry Computers & Semiconductors Wireless Mfg. Other Comms Environmental Forensics Food Academic & Government 4% 14% Aerospace & Defense Wireless R&D Broadband R&D/Mfg Petrochemical Pharma & Biotech Page 2 June 4, 2010

Agilent Genomics Portfolio DNA RNA acgh/ CNV CH 3 ChIP Target Enrich Sys. Splice Variants GE mirna Copy number Methylation Transcription Factors Targeted sample prep mrna isoforms mrna Micro RNAs Study chromosomal aberrations and measure gene copy number Map methylation patterns across and study effects on transcription Measure protein/dna interactions and to better characterize transcription, replication and repair. Enrich for genomic regions or transcripts for high throughput DNA sequencing Identify the splice forms of specific genes and study their effect on protein translation. Make high sensitivity measurements of gene transcription and correlate results with other genomic data Identify the presence of micrornas and measure the effect of knockouts and correlate this activity with gene transcription.

Agilent Bioinformatics Software A comprehensive suite of applications Transcriptome GeneSpring mirna, qpcr, Exon, Copy#, LOH, GWAS RNA Genome AGW ChIP, Methyl, CGH DNA Protein CH 2 OH Proteome Mass Profiler Pro Metabolome Mass Profiler Pro

GeneSpring: Data Analysis Solution for Omics Research

GeneSpring Value GeneSpring provides powerful, accessible statistical tools for fast visualization and analysis of expression and genomic structural variation data Designed specifically for the needs of biologists, GeneSpring offers an interactive desktop and enterprise computing environments that promotes investigation and enables understanding of microarray data within a biological context Developed on avadis from Strand Life Sciences, GeneSpring is part of Agilent s life sciences informatics portfolio for systems-level research Pellinore I/D Checkpoint Agilent Restricted March 5, 2009

GeneSpring in Genomics Research A Standard in Biological Interpretation GeneSpring has 7,800 references in Google Scholar and over 1,600 in peer reviewed publication GeneSpring has 10 years of history in RNA-based applications mrna expression analysis mirna analysis with TargetScan gene target identification Exon splicing analysis GeneSpring is an open-platform application Support Agilent, Affymetrix, Illumina and other vendors Supports custom format import Supports custom scripting using Jython and the R- Project for Statistical Computing (including Bioconductor) 8000 7000 6000 5000 4000 3000 2000 1000 0 Source: Google Scholar: 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 386 420 422

GeneSpring GX Platform Strengths Powerful Statistical Tools and Sophisticated Data Visualizations Biological Contextualization (pathway module) Strategic Partners Include:

GeneSpring Workgroup: Scalable Enterprise Solution

GeneSpring 11 Press Release Customer quote: Bruce Aronow Director of the Center for Computational Medicine Cincinnati Children s Hospital GeneSpring 11 represents a significant advance in data analysis software for life sciences. Here we see for the first time an all-wheel driving machine for multi-omics technologies that shape a new roadmap for integrative systems biology.

GeneSpring Platform Transformation Modular System for Integrated Biology Cytoscape Pathway Module Integration Module mrna mrna mirna qpcr CGH SNP mirna CNV GWAS CNV GWAS MPP CH3 ChIP DNAx NGS GeneSpring Platform (Common Code Base, Common Middle Tier, Visualizations, APIs, Installer) Enterprise (Workgroup) Server: Computation, Data Management, Collaboration Cluster Computing Grid Computing Utility Computing Cloud Computing

Multi-omic Analysis Cytoscape Cytoscape is an open source software platform for integrating, analyzing, and visualizing measurement data in their biological context. Cytoscape is a collaboration between University of California, San Diego Institute for Systems Biology Memorial Sloan-Kettering Cancer Center Institute Pasteur Agilent Technologies University of Toronto Gladstone Institute for Cardiovascular Disease University of California, San Francisco Unilever National Center for Integrative Biomedical Informatics freely available at http://www.cytoscape.org 80000+ downloads for 2.x release; 25,000 downloads in 2007 alone; 3500/month Currently 100 registered plugins, developed by leading research groups, freely available Community development of plugins strongly encouraged and actively supported by core development team.

Agilent Genomics Workbench Enabling Genomics Applications OLS acgh/ CNV CH 3 ChIP GX mirna Oligo Library Synthesis (OLS) Copy number Methylation Transcription Factors Gene Expression RNA interference Gene Silencing Protein Mutagenesis Whole Gene Synthesis Genome Partitioning Cancer Research Cytogenetics Population Studies Discover and monitor epigenetic changes that play a role in cellular processes Elucidate the role that protein-dna interaction plays in transcription, replication, and repair Explore gene transcription on a genome-wide basis across a variety of model systems Profile micrornas and explore the role they play in gene regulation earray Sample Manager Workflow Manager Feature Extraction DNA Analytics

AGW What is it? The Agilent Genomic Workbench (AGW) is a suite of desktop applications (client/server model) that provide Agilent customers with a single user environment to design microarrays, manage sample information, run feature extraction, perform quality and do analysis from scanned image onward. Agilent Genomic Workbench 6.0 earray XD Probe Design Probe Databases Catalog Designs Custom Designs Workbench Core Feature Extraction Sample Manager Workflow Manager Quality Module DNA Analytics Genome Browser CGH Analysis ChIP Analysis CH 3 Analysis

AGW FE 10.9 Workbench Core Feature Extractor Sample Manager Workflow Manager Quality Module Overview Sophisticated image analysis application that is used to generate raw intensity values from scanned microarray images New Features Merged database for FE, AGW and QC Tool Full version FE can be launched within AGW or outside of AGW Merged installer for FE, AGW Design file load once to support FE (grid template), Analytics and earrayxd. Automatic software version check and updates Migration tool to migrate previous custom protocol and metric sets Provide stats (like AF Hold, PMT Voltages) from Tiff Header to AGW

Superior Spot Finding and Pixel Outlier Rejection Raw Image All pixels Post-Processing Image Only pixels used in analysis are shown Cookie All pixels Cookie cutter After pixel outlier rejection

AGW Core Workbench Core Feature Extractor Sample Manager Workflow Manager Quality Module Sample Manager Enables users to easily associate meta data (patient/sample information) with individual slides. The meta data is then persisted through the analysis process. Workflow Manager Desktop utility that enables users to easily associate meta data (patient/sample information) with individual slides. The meta data is then persisted through the analysis process. Quality Module Array QC Tool: Quality control reporting tool that helps customer to assess microarray quality and analyze trends: calculates QC metrics and metrics sets, applies QC thresholds, plots QC trends Target Enrichment QC Tool: Quality control reporting tool that helps customer to assess pull down quality: QC reports; metrics for library complexity

Agilent Genomic Workbench 6.0 DNA Analytics earray XD (Desktop) Workbench Core Feature Extraction DNA Analytics Genome Browser Sample Manager CGH Analysis Workflow Manager ChIP Analysis Quality Module CH 3 Analysis Designed to examine data generated from DNA-based experiments. Analytics is comprised of modules that contain analysis packages for specific biological applications (i.e. CGH, ChIP, Methylation)

AGW DNA Analytics Analysis of Agilent Arrays acgh/ CNV CH 3 ChIP Copy number Cancer Research Cytogenetics Population Studies Methylation Discover and monitor epigenetic changes that play a role in cellular processes Transcription Factors Elucidate the role that protein-dna interaction plays in transcription, replication, and repair DNA Analytics CNV GWAS GeneSpring GE mirna Exon Proteomics Metabolomics DNA RNA Pro Page 20

earray.com earray XD

Agilent Genomics Portfolio DNA RNA acgh/ CNV CH 3 ChIP Target Enrich Sys. Splice Variants GE mirna Copy number Methylation Transcription Factors Targeted sample prep mrna isoforms mrna Micro RNAs Study chromosomal aberrations and measure gene copy number Map methylation patterns across and study effects on transcription Measure protein/dna interactions and to better characterize transcription, replication and repair. Enrich for genomic regions or transcripts for high throughput DNA sequencing Identify the splice forms of specific genes and study their effect on protein translation. Make high sensitivity measurements of gene transcription and correlate results with other genomic data Identify the presence of micrornas and measure the effect of knockouts and correlate this activity with gene transcription.

OpenLAB ELN for Genomics Create Analyze Helping customers: Increase data trace-ability Decrease time to find results Protect intellectual property Share

GeneSpring Support for Multiple Platforms qpcr ABI + Stratagene, Roche, BioRad, etc MICROARRAY (mrna and mirna) Agilent, Affymetrix, llumina,.gpr files; Any custom format SNP Arrays (Copy #, LOH, GWAS) Affymetrix and Illumina MASS SPEC Mass Profiler Professional application Agilent + Waters, Thermo, ABI, etc GeneSpring Page 24

LCMS GCMS The Agilent LCMS & GCMS Workflow separate detect peak find quantitate statistics identify pathways GC/MSD GC-QQQ AMDIS ID Browser Mass Profiler Professional LC-TOF/QTOF LC-QQQ MassHunter Qual MFE Page 25 September, 2009

Multi-omics Analysis in GeneSpring 11.5 (Summer 2010) Metabolomics Genotyping Alternative Splicing microrna qpcr Genomic Copy Number Proteomics Gene expression GeneSpring Page 26 June 10

Data Analysis Workflow in GeneSpring & MPP Transcription factor overexpressed! Start with raw data Find biological relevance of your entities Load data into GX or MPP Use powerful but easy-to-use statistics to filter the list GeneSpring Page 27 27 June 10