HigH-Content AnAlysis

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Cambridge Healthtech Institute’s TENTH Annual January 8-11, 2013 High-Content Analysis Anniversary High-Content Screening in 1536-Well Format 10:45-10:50 Chairperson’s Opening Remarks Richik N. Ghosh, Ph.D., Director, Research & Applications, Thermo Scientific High Content Products 10:50-11:15 Developing a High-Throughput High-Content Infrastructure and the Impact of 1536-Well HCS on BMS Drug Discovery Debra Nickischer, Research Scientist II, Cellular Systems, Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb There is a growing interest within the drug discovery industry to utilize more physiologically relevant cellular models in early hit-identification efforts, with the goal of identifying higher-quality drug candidates and enabling better prediction of liabilities. For high-throughput screening with large compound libraries, this translates to a need to enable sophisticated assay platforms such as high-content screening in a miniaturized, 1536- well microplate format. With focus on specific BMS programs, we will discuss considerations and challenges for developing high-throughput HCS capabilities and will outline innovative approaches to analyze and interpret the large volumes of content-rich data this platform provides. 11:15-11:40 A Miniaturized 1536-Well HCS Pipeline to Identify Small Chemical Compounds Improving Muscle Function Enrico Schmidt, Ph.D., Lab Head and Investigator III, Center for Proteomic Chemistry, Integrated Lead Finding 1, Novartis Pharma AG 11:40-11:55 New CCD Camera Technology for Sponsored by High-Content Screening Audra Ziegenfuss, Technical Product Manager, Thermo Scientific High Content Products As camera technology advances, higher sensitivity and better resolution are the results. We will be discussing a new CCD camera used in highcontent analysis and comparing it to current technologies being used in the high-content space. Sponsored by 11:55-12:10 pm Enabling High-Throughput HCS with the Cell Insight Debra Nickischer, Research Scientist II, Cellular Systems, Molecular Sciences and Candidate Optimization, Bristol-Myers Squibb We will discuss how BMS is utilizing the Thermo Scientific CellInsight HCS Platform in Lead Discovery. We will describe our automation configurations with the Thermo Scientific Orbitor plate handlers; how the CellInsights have enabled our high-throughput, high-content screens; and the impact on BMS drug discovery. 12:10- 12:25 New Developments in High Sponsored by Content Imaging Systems for Faster and More Efficient Screening HaiGuang Zhang, Ph.D., Senior Application Consultant, GE Healthcare Rapid acquisition without compromising on image quality is essential for successful high content screening, particularly in high well-density formats. GE Healthcare is continuing to push the boundaries of HCS by incorporating the latest advances in hardware and software technologies for optical imaging. We will discuss new components and features of the IN Cell Analyzer systems that are enabling more rapid, robust and efficient hit identification and assessment. 12:25-12:40 Sponsored Presentation (Opportunity available. Contact Katelin Fitzgerald at kfitzgerald@ healthtech.com or 781-972-5458.) 12:40-1:45 Enjoy Lunch on Your Own High-Content Image and Data Analysis 10:45-10:50 Chairperson’s Opening Remarks 10:50-11:15 Flat Field Correction and Multi-Parametric Regression Models for High-Content Analysis Peter Horvath, Ph.D., Data Analysis Specialist, Light Microscopy and Screening Center, ETH Zurich 11:15-11:40 Content-Based Searching of Bioimage Databases Robert F. Murphy, Ph.D., Professor, Computational Biology and Biological Sciences, Biomedical Engineering and Machine Learning; Director, Ray and Stephanie Lane Center for Computational Biology, Carnegie Mellon University We have developed OMERO.searcher as the first of a series of open source tools that can augment the capabilities of a bioimage database system such as OMERO. OMERO.searcher Server can be installed on top of an OMERO database to allow both internal and external users to perform image content searches. These searches can be done to find images similar to a selected image (or images) already in the database, or using images on a user’s own computer. External users can also use OMERO.searcher Local Client to search one or more remote databases using similarity to local images, and searching of databases that use systems other than OMERO can also be easily enabled. I will discuss our experience with adapting other advanced image analysis tools for use with OMERO databases. 11:40-12:05 pm Making an Individual Cell’s Voice Heard: The Beauty of High-Content Screening Tiao Xie, Ph.D., Leader, Image and Data Analysis Core (IDAC), Harvard Medical School A wide spectrum of image analysis tools/approaches have been utilized at IDAC to quantify the image datasets from the diverse image-based screening assays. The recent development of commercial image analysis packages has enabled us to robustly analyze data generated from the more traditional image-based assays such as cell viability, mitotic index and protein expression/translocation assays. However, some assays that target very specific morphological changes of whole cells or sub-cellular structures require more customized analysis solutions to extract specific information from the images. Moreover, the massive scale of image datasets generated from high-throughput screens also call for integrated data management approaches, including image storage, sharing, visualization, analysis and secondary data handling. Several successful stories will be presented to demonstrate our high-content screening capacity at Harvard, from image acquisition/storage, to high-content analysis and data visualization. 12:05-12:20 Complex Challenges in the Field Sponsored by of Cellular Level Research Require NEW Paths in Your Road to Discovery Robert Graves, Ph.D., Senior Application Specialist, GE Healthcare For today’s highly automated systems for image acquisition requires insight into cells and intracellular components. The tools you need for everyday assays are complex, unique applications requires a comprehensive package of image analysis tools for a broad range of imaging experiments. Come and learn about our highly adaptive software configured for a range of skills and experience to meet your challenges in the modern lab. 12:20-12:35 Sponsored Presentation (Opportunity available. Contact Katelin Fitzgerald at kfitzgerald@ healthtech.com or 781-972-5458.) 12:35-1:45 Enjoy Lunch on Your Own 4 | High-Content Analysis HighContentAnalysis.com
Cambridge Healthtech Institute’s TENTH Annual January 8-11, 2013 High-Content Analysis Anniversary HCA for Toxicity Assessment 1:45-2:10 High-Content Screening of Zebrafish Embryos for Drug Safety Assessment Jyotshna Kanungo, Ph.D., Principal Investigator, Lead Scientist, Zebrafish HTS Laboratory, National Center for Toxicological Research, FDA Zebrafish embryos are being routinely used in chemical toxicity assessments. Since these tests require minimal amounts of test compounds, test durations are less time-consuming than typical toxicity tests, and multi-parametric high-content assays based on a variety of sub-lethal endpoints can easily be performed including those useful for the assessment of a chemical’s teratogenicity. We have developed several endpoints for high-content analysis of drug effects on the zebrafish embryos. In one approach, using multi-well plates, a high-content automated imaging procedure is employed to measure axon length in zebrafish embryos in vivo to screen for drug effects and determine dose levels that are developmentally toxic. Automated fluorescent image acquisition of the transgenic embryos is performed in vivo with embryos arrayed in 384-well plates, and post-acquisition image analysis provides average axon lengths in the control and experimental groups. 2:10-2:35 Removing the Edge Effect Limitation of Cytotoxicity Testing Peter J. O’Brien, D.V.M., Ph.D., Veterinary Clinical Pathologist, Pathology, University College Dublin The edge effect is one of the most limiting factors in performing cytotoxicity tests conducted over multiple days. Microenvironments of wells at the edges of microtiter plates can restrict cell growth and function and response to treatment. This effect is also found, although to a lesser extent, at the wells near to the edge and found to a greater extent with wells at plate corners. A recently-developed microtitre plate has largely eliminated this adverse effect, with a proprietary method for maintaining a constant microenvironment across all wells. The positive impact of this development on sample throughput, measurement precision, and accuracy of cytotoxicity assessment will be demonstrated. 2:35-3:00 Contribution of Physicochemical Properties to Toxicity Shuyan Lu, Principal Scientist, Drug Safety Research & Development, Pfizer We examined the relationship between physicochemical properties, such as partition coefficient (clogP), topological polar surface area (TPSA), acid dissociation constant (pK(a)), and in vitro mechanistic endpoints generated using a high-content imaging approach. We demonstrate in our initial analysis that compounds with clogP>2 and pK(a)>5.5 flagged more endpoints than compounds with clogP ≤ 2 and pK(a) ≤ 5.5. When this knowledge was applied to eight different mechanistic cytotoxicity endpoints (cell loss, apoptosis, ER stress, DNA fragmentation, mitochondrial potential, nuclear size, neutral lipids/steatosis and lysosomal mass), we found that compounds with such properties preferentially flagged in the lysosomal endpoint. We also saw a slight enrichment of such compounds in the endpoints cell loss, DNA fragmentation and nuclear size. In addition we demonstrated the contribution of physicochemical property to cardiotoxicity induced by imatinib. 3:00-3:15 Cardiotoxicity of Oncology Drugs: Sponsored by High Content Analysis of Kinase Inhibitors in a Human Stem Cell Derived Cardiomyocyte Model Nick Thomas, Ph.D., Principal Scientist, Cell Technologies, GE Healthcare Industrial scale production of cardiomyocytes from human stem cells provides the potential to develop novel and improved physiologically relevant and human-predictive assays for cardiac drug liabilities. We have used a four color multi-parameter assay on IN Cell Analyzer to profile the phenotypic effects of a large panel of anticancer drugs currently in clinical use and in development. Multi-parameter profiling and clustering provides an efficient means to characterize cardiotoxic drug actions and to gain insights into mechanisms of cell injury. Image Analysis Technology Showcase 1:45-2:15 New Developments in Accelerating Sponsored by the High-Content Screening Work Flow Grischa Chandy, Product Manager, Cellular Imaging, Molecular Devices, LLC Evan F. Cromwell, Ph.D., Director, Research, Molecular Devices, LLC Next-generation high-content tools for imaging offer automated techniques for modeling diseases and predictive toxicology. We will present examples of multi-parametric assays for testing the effects of compounds in a variety of assays and highlight the new innovative software that provides step-by-step assistance for designing customized, reusable, and distributable analysis algorithms. 2:15-2:45 Get the Big Picture in Phenotypic Sponsored by Screening for Drug Discovery Oliver Leven, Head, Professional Services, Genedata High Content Screening is now routine in drug discovery, but integration of the HCS dataflow is still problematic. HCS images from phenotypic screening are reduced to numerical results and then are stored in isolated, instrument-specific image data management systems. Often there is no integration with central result data warehouses, and assay and compound results may be stored without any reference back to original image data. We will present a data management workflow that starts after initial image capture, supports data analysis and interpretation, and allows result mining using past experiments and maintains references to well images. 2:45-3:15 Analysis and Reporting for High- Sponsored by Content Screening with FCS Express 4 Image Cytometry by De Novo Software David Novo, Ph.D., President & CEO, De Novo Software De Novo Software has developed premier analysis and reporting tools for research and clinical flow cytometry for a decade. Leveraging this experience, we developed an image cytometry package for HCA. A flow cytometry analysis environment for image cytometry data allows fully interactive data and image review at a single-cell level. Create sophisticated reports with 1-click. Sponsored by 3:15-4:15 Refreshment Break in the Exhibit Hall with Poster Viewing PRESENT A POSTER AND SAVE $50! Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. To secure a poster board and inclusion in the conference materials, your abstract must be submitted, approved and your registration paid in full by November 16, 2012. Register online, or by phone, fax or mail. Please indicate that you would like to present a poster. Once your registration has been fully processed, we will send an email with a unique link and instructions for submitting your abstract using our online abstract submission tool. Please see below for more information. Reasons you should present your research poster at this conference: • Your poster will be exposed to our international delegation • Receive $50 off your registration • Your poster abstract will be published in our conference materials • Your research will be seen by leaders from top pharmaceutical, biotech, academic and government institutes Note: Posters should be portrait orientation, with maximum dimensions of 36 inches wide (3 feet) x 48 inches high (4 feet). HighContentAnalysis.com High-Content Analysis | 5
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