GE Healthcare. Visualize Analyze. Realize. IN Cell Miner HCM Data management for high-content analysis and screening
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1 GE Healthcare Visualize Analyze Realize IN Cell Miner HCM Data management for high-content analysis and screening
2 Managing the data mountain High-content analysis (HCA) provides quantitative insights in to cellular events and processes. However, increasing productivity creates new challenges for data management. IN Cell Miner HCM is a client-server based application that enables organizations to manage and mine these valuable assets effectively. HCA measures biochemical and morphological changes in cells both rapidly and accurately. However, each year, HCA/HCS systems, such as the IN Cell Analyzer 1000 can produce: 38 TB of data 12 million images 30 billion measurements from individual cells Once annotated with detailed experimental conditions, this mountain of interconnected data becomes a valuable asset for basic research and drug discovery that can be mined for an understanding of cellular function or drug action. Meta-data Provide context Quantitative results Drive decisions Images Revisit raw data Fig 1. The HCA data mountain. Images make up most of the storage volume generated by HCA systems. The remaining storage comprises numerical results derived from images by analysis algorithms, and metadata or annotations, which are used to organize, search, and retrieve information. 1
3 Streamlining the HCA data flow IN Cell Analyzer 1000 automatically acquires high-quality images from cell-based assays. These images are then analyzed by IN Cell Investigator software, providing quantitative data for downstream analysis and decision making using Spotfire DecisionSite and other software tools. IN Cell Miner HCM is a client-server based content management solution that complements the IN Cell Analyzer instrument and IN Cell Investigator software. It streamlines the HCA data flow by providing a central repository for raw image data and numerical results, placing them into a searchable context. Stored data can be accessed via a feature-rich HCA-specific desktop client while EMC s proven Documentum content server application ensures reliability, scalability, and performance. The result is a system that can easily deal with the unprecedented amounts of data generated by HCA. Questions, data, and, materials (eg cells and compounds) Downstream processing and decision making Annotations Search Import/Export Project definitions IN Cell Miner HCM IN Cell Analyzer Image analysis IN Cell Investigator Data analysis Fig 2. IN Cell Miner HCM enables the storage, retrieval, and transfer of data across the IN Cell analysis platform. 2
4 Getting started Scientists interact with IN Cell Miner HCM through a rich, full-featured desktop client. The interface is tailored specifically to the HCA workflow and provides easy access to images, annotations, and numerical data. The IN Cell Miner HCM homepage (Fig 3) includes a ribbon bar at the top of the page that provides direct access to all projects, common queries, and key functions. This makes it easier for new users to get started while expert users have access to more advanced functions. From the homepage you can: Resume your work after your last session Import new data Access existing data through projects or queries IN Cell Miner HCM uses different Aspects to view and zoom into your data. In addition to the homepage there are Project, Plate, Well, and Cell Aspects, with each Aspect providing review tools appropriate to the level of data (Fig 4). Fig 3. The client performs the bulk of any data processing operations itself enabling a high level of performance and functionality. Fig 4. Well Aspect showing some key interface elements (clockwise from left): Guided Query bar for querying data sets; Ribbon bar for access to key functions; Context Viewer for viewing detailed properties, charts, and images; flexible data table for numerical results; and central data display for plate maps or thumbnail images. 3
5 Getting organized Data can be navigated using a multilevel hierarchy that reflects the project structure (Table 1). Such a hierarchy makes it easier to review related results when looking for promising candidates. Table 1. Project hierarchy Level Project Screen Run Plate Well Image stack Analysis results Key functions Holds all data belonging to one research project. Access rights are managed at this level. User-defined collection of multiple screens. User-defined collection of multiple runs. A screen might hold all data belonging to one aspect of the project. User-defined collection of multiple plates. A run might hold data form all plates read in one run of the instrument. The plate refers to the physical object that has been used for imaging. The plate has undergone some sort of treatment and holds specific samples. A plate can hold multiple image stacks (e.g., different time points, exposure times, and associated results). Physical location on plate, holds specific sample and treatment conditions (e.g., compounds and concentrations). A set of images acquired from one plate in one operation using the same acquisition protocol. Images have five possible dimensions: x, y, z, channel (wavelength), and time. Numerical results derived from a specific image stack using the same analysis protocol. The multilevel hierarchy within IN Cell Miner HCM allows you to create a screen containing all runs from a variety of assay types in one place. You can then search within your defined project and review images, charts, and component properties at the required level. Store different types of data including images, protocols, results, and annotations Manage data at project, screen, run and plate level Associate protocols, materials or compound list with the appropriate project levels Associate multiple image stacks with one plate Associate results from different analysis protocols with one set of images Fig 5. The IN Cell Miner HCM Project Aspect allows the user to set up and define the hierarchy of their projects. Shown here is a simple project (orange) with one screen (purple) and one run (yellow) that holds ten plates (blue). Green indicates the corresponding acquisition protocols. The navigation bar on the left allows easy navigation around large projects whereas the central Project Canvas provides a visual representation of the project. Properties of selected objects are displayed on the right-hand panel. 4
6 Annotating and retrieving data IN Cell Miner HCM stores data based on concepts pioneered by open-standard communities such as the OME (Open Microscopy Environment) and MIACA (Minimum Information About a Cellular Assay). Descriptions of experimental detail can be annotated to HCA data allowing assay results to be searched and placed in to biological context. Rich annotations of assay conditions such as gene names and incubation temperatures allow searching for data in a variety of ways and increase the possibility of uncovering both expected and unexpected correlations. IN Cell Miner HCM uses a Guided Query bar for interactive data retrieval (Fig 6) and it is possible, for example, to query data based on the following. Plate, assay, or analysis names Hierarchy level Experimental conditions (e.g., compounds, reports, cell lines) Cell measures (e.g., cell number, nuclear size) Once data has been retrieved, it can be reviewed using table and graphing functions in the IN Cell Miner HCM or transferred for further visualization and analysis to applications such as IN Cell Investigator, Spotfire DecisionSite (Fig 7) and Microsoft Excel. Fig 6. Plate Aspect showing the Guided Query bar on the left. The Ribbon bar is at the top, and the Property Pane on the right. The central part of the page can be used to display plate heat maps (shown) or a list view. The Plate Aspect allows large numbers of plates to be reviewed. Fig 7. Spotfire DecisionSite screenshot showing different visualizations from a sirna knockdown experiment. The 3D view allows clear identification of those sirna that cause a distinct phenotype. 5
7 Securing productivity IN Cell Miner HCM is a client-server application based on the EMC Documentum Content Server 5.3 OEM Edition and takes advantage of its proven architecture and advanced content management features. IN Cell Miner HCM provides: Controlled data access by defining security levels and user rights Life cycle management for project data Scalability from small workgroups to large enterprise IN Cell Miner HCM is Designed for Documentum accredited, a certification that signifies IN Cell Miner HCM: Meets the stringent quality levels expected for Documentum-based solutions. Follows best practices for design, development, deployment, and support to enable high productivity from out of the box. Employs Documentum services correctly and only utilizes supported interfaces to enable customers with existing Documentum installations to integrate IN Cell Miner HCM seamlessly with other mission-critical applications. IN Cell Miner HCM manages data ranging from workgroup environments to enterprise-wide applications. It supports a variety of storage systems ranging from direct attached RAID arrays and network attached storage devices to EMC CENTERA CAS content addressed storage suited for situations when regulatory compliance and data security are paramount. Fig 8. The user interacts with IN Cell Miner HCM on the client PC through the applications layer. The interface channels communication between the desktop application and the server-based content services, which organize and deliver data to and from the repository that stores and provides access to HCA data. Repository 6
8 Supporting performance IN Cell Miner HCM is supported by the specialist IN Cell support team and can be supported remotely via Bio Insite. Bio InSite is a secure digital connection between GE Healthcare professionals and your system. It is an interactive help line to accelerate knowledge sharing and simplify troubleshooting so you can keep working smoothly. This easy-to-use technology utilizes a highly secure connection between GE Healthcare and your system. It is easy to implement and requires no modification to your IT network. With Bio InSite, you can focus on science, unlocking the full capability of your IN Cell Miner HCM installation, and boosting productivity in your laboratory. IN Cell Miner HCM Project definition Import/Export Annotations Search Application layer Web services Interface layer Documentum Business Object Framework Documentum Foundation Classes Documentum Content Server Content services layer 7
9 Technical specifications We provide a fully validated preconfigured hardware solution to run the Document Content Server application. This ensures an optimal user experience even under high data loads. The HP ProLiant DL380G5 Server provides the performance and high uptime required in a professional environment. Ordering information For additional product information or to request a quotation, please contact your GE Healthcare Sales Specialist. Server application for Documentum Content Manager We strongly recommend installing the D5 Content Manager only on the following dedicated server supplied by GE Healthcare in order to ensure optimal performance and support experience: HP DL 380 G5 Proliant Server 2 Quad-Core Intel Xeon E5410 processors (2.33 GHz, 1333 MHz FSB, 2 4 MB L2) 8 GB RAM 3 72 GB SAS system hard drives HP StorageWorks 70 Modular Smart Array with GB 10 krpm SAS hard drives (2 TB total storage) ProCurve 24 port gigabit network switch HP R3000 uninterrupted power supply (UPS) HP 14U S10614 Rack Cabinet PC specification for desktop client software Recommended specifications: Windows XP Professional SP2 PC-compatible with 2 Intel Xeon dual-core processors High-resolution graphics display (minimum of 1024 x 768 x 24 bits) 2 GB RAM for single core, 3 GB for dual core, and 4 GB for 4 cores is recommended The paging file should have match RAM size as indicated above Active network access to the IN Cell Miner HCM Server (gigabit network preferred) Active internet access for automatic updates Microsoft Internet Explorer 6.0 Minimum specifications: Windows XP (Professional or Server version) PC-compatible with a Pentium IV microprocessor High-resolution graphics display (minimum of 1024 x 768 x 24 bits) 1 GB RAM The paging file should have a minimum size of 1 GB Active network access to the IN Cell Miner HCM Server 8
10 GE, imagination at work, and GE monogram are trademarks of General Electric Company. Bio Insite is a trademark of GE Healthcare companies. All third party trademarks are the property of their respective owners General Electric Company All rights reserved. First published July 2008 GE Healthcare Bio-Sciences AB Björkgatan Uppsala Sweden GE Healthcare UK Ltd Amersham Place Little Chalfont Buckinghamshire HP7 9NA UK GE Healthcare Europe GmbH Munzinger Strasse 5, D Freiburg Germany GE Healthcare Bio-Sciences KK Sanken Bldg , Hyakunincho Shinjuku-ku, Tokyo Japan For contact information for your local office, please visit GE Healthcare Bio-Sciences Corp 800 Centennial Avenue P.O. Box 1327 Piscataway, NJ USA AA 07/2008
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