Agilent CytoGenomics 1.5 For Detection of CNC, LOH and UPD Not approved for use in diagnostic procedures Slide 1 out of 15

Agilent CytoGenomics 1.5 Value Proposition Streamlining the Cytogenetic data analysis workflow for CNC (copy number changes) and/or cnLOH (copy neutral Loss of Heterozygosity) / UPD (uni-parental disomy) detection of samples processed on Agilent SurePrint G3 CGH and CGH+SNP Microarrays. Value Proposition: To enable the Cytogenetic Researcher to analyze a normal constitutional CGH (or CGH+SNP) sample in less than 5 minutes, including report generation. Not approved for use in diagnostic procedures Slide 2 out of 15

Agilent CytoGenomics 1.5 System specs Client/server system with database. Possible configurations: multiple clients can access central database simultaneously. server Client(s) and Server (Database)on separate machines Client 1 Client 2 Client and Server (Database) on same machine Not approved for use in diagnostic procedures Slide 3 out of 15

Agilent CytoGenomics 1.5 System specs Supported OS for the PC: XP, Windows 7. Supported OS for the Mac: OS X Leopard, OS X Snow Leopard. Supported on both 32 and 64 bit machines. Minimum of 4GB of memory needed for 32 bit (8GB for 64 bit). FE (Feature extraction) is integrated component of CytoGenomics software. Not approved for use in diagnostic procedures Slide 4 out of 15

1. Configure analysis method Agilent CytoGenomics 1.5 Workflow based system Preloaded default workflows available Customizing your workflow: Day to day usage: Technician (manual) / Auto-processing mode Upload TIFF images Map array to sample ID and other attributes Engage configured workflow to run FE and analysis Scientist Manual analysis / triage the sample and sign off Generate the CytoReport 1. Configure analysis method 2. Configure CytoReport 3. Configure Workflow Not approved for use in diagnostic procedures Slide 5 out of 15

Agilent CytoGenomics 1.5 Streamlined data analysis and reporting for Cytogenetic research labs Fast 5-minute data analysis and report generation for a normal constitutional sample. Convenient input and output support allowing for integration with LIMS. Cyto report Manual analysis & sign off Run data analysis Sample info Laboratory LIMS Not approved for use in diagnostic procedures Slide 6 out of 15

Measuring SNPs using restriction enzymes Genotype SNPs using restriction digestion (Alu/Rsa) We measure the copy number of one allele at each SNP site relative to a known reference Regions of LOH are located by finding genomic regions with a statistically significant scarcity of heterozygous calls ~5-10 Mb LOH/UPD resolution across the entire genome Not approved for use in diagnostic procedures Slide 7 out of 15

Agilent CytoGenomics 1.5 Powerful algorithms for calling CNC, LOH and UPD Log2 ratio of intensities to call CNCs No. of uncut alleles to call LOH/UPD Feature Extraction AA AB BB ADM-1 ADM-2 SNP CN & LOH GC correction Not approved for use in diagnostic procedures Slide 8 out of 15

Agilent CytoGenomics 1.5 Example: Consanguineous Sample SNP data detects blocks of cnLOH throughout the genome AA AB BB Not approved for use in diagnostic procedures Slide 9 out of 15

Agilent CytoGenomics 1.5 Example: Sample with deletion on chr9 p-arm One copy deletion confirmed by SNP data A A B AA AB BB Not approved for use in diagnostic procedures Slide 10 out of 15

Agilent CytoGenomics 1.5 Sample Triage – Access to external databases Upload custom tracks Not approved for use in diagnostic procedures Link out from genes associated with aberrations to external Databases: DGV, OMIM, Entrez Link out to and compare aberrations in DGV and UCSC genome browser Preloaded tracks: DGV-CNV Not approved for use in diagnostic procedures Slide 11 out of 15

Agilent CytoGenomics 1.5 Sample Triage – Sample and Aberration annotation Add notes to sample Add notes to aberrations Not approved for use in diagnostic procedures Classify aberrations Edit aberrations Suppress aberrations Not approved for use in diagnostic procedures Slide 12 out of 15

Agilent CytoGenomics 1.5 Sample Triage – Using the CytoGenomics in house Database Auto updated tracks based on aberration classification in CytoGenomics Database Showing number of samples with overlapping aberrations in database Not approved for use in diagnostic procedures Right click on Classification allows query for overlapping aberrations in database: results will be shown as new track along the gene view Not approved for use in diagnostic procedures Slide 13 out of 15

Agilent CytoGenomics 1.5 Multi Sample View Sample A Sample B Sample C Comparing 2 or more samples side by side Not approved for use in diagnostic procedures Slide 14 out of 15

Agilent CytoGenomics 1.5 Key feature summary Easy 5 minute data analysis for constitutional normal sample, including report generation. Powerful algorithms for detecting CNC, cnLOH and UPD. Interval classification and database queries for similar aberrations. Workflow Automation Mode for automatic processing of TIFF images and report generation. Linking out to external databases such as OMIM, DGV and Entrez. Data upload to ISCA DB via Cartagenia bench. Help videos available inside the software explaining key functionality. Download CytoGenomics free trial @ https://earray.chem.agilent.com/earray/ Not approved for use in diagnostic procedures Slide 15 out of 15