Clinical Genomics Joint with RCRIM

1. Clinical Genomics Joint with RCRIM Amnon Shabo Joyce Hernandez Mukesh Sharma

2. AGENDA • Gene Expression CMET Overview • Genetic Reports CDA Ballot Overview • Gene Expression DAM Update • Generic Assay Overview • Specimen Model

3. Gene Expression CMET Overview

4. Gene Expression DAM Update • Currently reviewing results of the last ballot • Next steps: • Finish NCI Generic Assay (IRWG) • Changes to GE DAM • Add “generic” classes from Generic Assay • Bring over additional BRIDGE Classes • Apply suggested changes from the ballot (use case, BRIDG compatibility)

5. Clinical Genomics DAM (50,000 foot level view) Genetic Variation Bio-Specimen Gene Expression

6. Color Coding Scheme

7. CG DAM Views • Process Models • Specimen Handling and Collection (based on NCI public protocol) • Genomcis Testing Process (high level) • Future – interaction diagrams for message flows per Use Case • Gene Expression – Whole Model • Bio-specimen • Experiment Definition (Gene express specific protocol, not entire study) • Array Design • Common Classes • Data • Relationships

8. Generic Assay Overview ExperimentalItem Equipment * Protocol * * Software * Study Experiment Data * * * -Study may include other Studies -Study may be composed of many Experiments -Experiment may include other Experiments -Experiment may involve multiple ExperimentalItems -Experiment may be based on multiple Protocols -Experiment may be performed using multiple Equipment -Experiment may be performed using multiple Software -Experiment may produce multiple Data (Output) 8

9. Generic Assay Overview • Equipment: • -Thermacycler • -gel apparatus • camera/image system • Affymetrix Fluidics WashStation 450 • Affymetrix GS3000 scanner ExperimentalItem: -Project-specific specimen set Protocol: -Affymetrix Cytogenetics Assay Protocol -Affymetrix Protocol for One-Cycle cDNA Synthesis ExperimentalItem Equipment * Protocol * • Software: • -image acquisition application • Agilent 2100 Operating Software • GCOS application * Study: - Gene expression analysis of tumor/non-tumor sample pair Software * Study Experiment Data * * * • Examples of Data (ie., Output): • A_U133P2_cDNA • A_U133P2_cDNA_gel_tif • A_U133P2_cDNA_gel_doc • A_U133P2_SpecimenHybChipWashed (ready for stain and wash) • A_U133P2_Specimen_dat • A_U133P2_Specimen_cel • A_U133P2_Specimen_chp (data file with genotypes) Experiment: -Affymetrix U133P2 Gene Expression -Affymetrix U133P2 Analysis -Specimen definition information entry (might be a component of Affymetrix U133P2 Gene Expression) -Total RNA extraction and QC (might be a component of Affymetrix U133P2 Gene Expression) -cDNA synthesis and cleanup -U133P2 array scan (GCOS: create *.dat and create (.dat to) *.cel) -GCOS U133P2 Gene Expression Analysis (might be a component of Affymetrix U133P2 Analysis) 9

10. Generic Assay Overview Equipment: An object intended for use whether alone or in combination for diagnostic, prevention, monitoring, therapeutic, scientific, and/or experimental purposes. For example, ….mass spectrometer, PCR machine, microscope, pH meter = Proposed last week Equipment Protocol: A rule which guides how an activity should be performed. * Software Protocol * * ExperimentalItem: Items used in the execution of an experiment: specimens - samples either taken from nature or created for the purpose of study and which are to be the subject of an experiment, and reagents and supplies which will be used in the execution of an experiment. It is not instruments, analysis tools, and general-purpose resources (common reagents, lab equipment, personnel). ExperimentalItem * Study Experiment * Experiment: A coordinated set of actions and observations designed to generate data, with the ultimate goal of discovery or hypothesis testing. Study: A detailed examination or analysis designed to discover facts about a system under investigation. Systems may include intact organisms, biologic specimens, and natural or synthetic materials. Data * -Study may include other Studies -Study may be composed of many Experiments -Study may be performed according to multiple Protocols -Experiment may include other Experiments -Experiment may involve multiple ExperimentalItems -Experiment may be performed according to multiple Protocols -Experiment may be performed using multiple Equipment -Experiment may be performed using multiple Software -Experiment may produce multiple Data (Output) -Experiment may be performed on Data (data an input for analytical experiment) -Protocol may include other Protocols -Protocol may specify Equipment -Protocol may specify Software -Equipment may specify Software Data: A collection or single item of factual information, derived from measurement or research, from which conclusions may be drawn. For example, an image, a .DAT, or .CEL file. ProcessedData: Data derived from other data. For example, image annotations derived from an image, or the outcome of running a .CEL file through an analytical tool. The notion of what is data (vs. processed data) is defined by community consensus and may be mutable. Some may consider the .DAT file to be data, and that the .CEL file is processed, while others may consider the .CEL file itself to be data (unprocessed). 10

11. Generic Assay Overview • Notes: • ProcessedData has association to Finding; not included on the diagram to keep things focused • Isn’t the result of an analytical experiment what we’ve called ProcessedData? • Do we need to have distinction between Data and ProcessedData? Can we have self association on Data to handle both in the DAM • Software needs to be defined • What about association from ExperimentalItem to ExperimentalStudy?

12. Specimen Model Overview(Mukesh Sharma)