Agilent Genomics Software Future Directions

Michael Rosenberg, PhD Director, Genomics Software Agilent: A Focused Measurement Company Serving Diverse End Markets

Electronic Measurement Bio-Analytical Measurement 2008 Revenue: $3.6 Billion 2008 Revenue: $2.2 Billion

General Purpose Communications Chemical Analysis Life Sciences 37% 25% 20% 18%

Other General Computers & Forensics Industry Semiconductors Wireless Mfg. Other Comms Environ- Academic & Government mental Food 4%

14%

Aerospace Broadband & Defense Wireless R&D R&D/Mfg Petrochemical Pharma & Biotech

Page 2 June 4, 2010 Agilent Genomics Portfolio

DNA RNA

Target aCGH/ CH ChIP Splice miRNA CNV 3 Enrich Variants GE Sys.

Transcription Targeted sample prep mRNA Copy number Methylation mRNA Micro RNAs Factors isoforms

Make high sensitivity Identify the presence Study chromosomal Map methylation Measure protein/DNA Enrich for genomic Identify the splice measurements of of microRNAs and aberrations and patterns across and interactions and to regions or transcripts forms of specific gene transcription and measure the effect of measure gene copy study effects on better characterize for high throughput genes and study their correlate results with knockouts and number transcription transcription, DNA sequencing effect on protein other genomic data correlate this activity replication and repair. translation. with gene transcription. Agilent Bioinformatics Software A comprehensive suite of applications

Transcriptome Genome GeneSpring AGW miRNA, qPCR, Exon, ChIP, Methyl, CGH Copy#, LOH, GWAS RNA DNA

CH2OH Protein

Proteome Metabolome Mass Profiler Pro 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

Source: Google Scholar: 8000

GeneSpring has 7,800 references in Google Scholar 7000 and over 1,600 in peer reviewed publication 6000

5000 GeneSpring has 10 years of history in RNA-based applications 4000 • mRNA expression analysis 3000 • miRNA analysis with TargetScan gene target 2000 identification 1000 • Exon splicing analysis 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 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- 386 Project for Statistical Computing (including Bioconductor) 420 422 GeneSpring GX Platform Strengths

Powerful Statistical Tools and Sophisticated Biological Contextualization (pathway Data Visualizations 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 NGS CH3 DNAx mRNA CGH SNP MPPMPP ChIP mRNA miRNAqPCR GWAS miRNA CNVCNV GWAS

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 a collaboration between Cytoscape is an open source software platform for University of California, San Diego

integrating, analyzing, and visualizing Institute for Systems Biology

measurement data in their biological context. 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

aCGH/ OLS CNV CH3 ChIP GX miRNA

Oligo Library Copy Methylation Transcription Gene RNA Synthesis (OLS) number Factors Expression interference • Cancer Research Discover and monitor Elucidate the role that Profile microRNAs and • Gene Silencing Explore gene • Cytogenetics epigenetic changes protein-DNA explore the role they • Protein Mutagenesis transcription on a • Population Studies that play a role in interaction plays in play in gene regulation • Whole Gene Synthesis genome-wide basis cellular processes transcription, • Genome Partitioning across a variety of replication, and repair model systems

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

eArrayXD 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 CH3 Analysis Workbench Core Feature Sample Workflow Quality Manager Manager Module AGW– FE 10.9 Extractor

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 Workbench Core Feature Sample Workflow Quality Extractor Manager Manager Module AGW Core

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

eArrayXD (Desktop)

Workbench Core Feature Sample Workflow Quality DNA Extraction Manager Manager Module Analytics DNA Analytics Genome CGH Analysis ChIP Analysis CH Analysis Browser 3

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/ CH ChIP CNV 3

Copy number Methylation Transcription Factors • Cancer Research Discover and monitor Elucidate the role that • Cytogenetics epigenetic changes that protein-DNA interaction • Population Studies play a role in cellular plays in transcription, processes replication, and repair

DNA Analytics

GeneSpring GE CNV miRNA Proteomics GWAS Exon Metabolomics

DNA RNA Pro

Page 20 eArray.com

eArrayXD Agilent Genomics Portfolio

DNA RNA

Target aCGH/ CH ChIP Splice miRNA CNV 3 Enrich Variants GE Sys.

Transcription Targeted sample prep mRNA Copy number Methylation mRNA Micro RNAs Factors isoforms

Make high sensitivity Identify the presence Study chromosomal Map methylation Measure protein/DNA Enrich for genomic Identify the splice measurements of of microRNAs and aberrations and patterns across and interactions and to regions or transcripts forms of specific gene transcription and measure the effect of measure gene copy study effects on better characterize for high throughput genes and study their correlate results with knockouts and number transcription transcription, DNA sequencing effect on protein other genomic data correlate this activity replication and repair. translation. with gene transcription. OpenLAB ELN for Genomics Analyze Create

Helping customers:

•Increase data trace-ability •Decrease time to find results •Protect intellectual property Share GeneSpring Support for Multiple Platforms

MICROARRAY (mRNA and miRNA) – Agilent, Affymetrix, llumina, – .GPR files; Any custom format qPCR – ABI + Stratagene, Roche, BioRad, etc

SNP Arrays (Copy #, LOH, GWAS) – Affymetrix and Illumina

MASS SPEC

– ‘Mass Profiler Professional’ application – Agilent + Waters, Thermo, ABI, etc

GeneSpring

Page 24 The Agilent LCMS & GCMS Workflow

separate peak find statistics identify pathways

detect quantitate GCMS GC/MSD AMDIS GC-QQQ

ID Browser

Mass Profiler

Professional LCMS LC-TOF/QTOF MassHunter Qual LC-QQQ 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 over- expressed!

Start with raw data

Find biological relevance Load data of your entities into GX or MPP

Use powerful but easy-to-use statistics to filter the list

GeneSpringGeneSpring

Page 27 27 June 10