2013 Archived Content

High Content Analysis - Day 1


Advanced CourseUser Group Meetings | Main Program Wednesday | Main Program Thursday
Live-Cell Imaging Workshop | Download PDF 

 

Wednesday, January 9, 2013   Main Conference

7:30-8:30 am Conference Registration

8:30-8:40 Welcome Remarks from Conference Director

Julia Boguslavsky, Executive Director, Conferences, Cambridge Healthtech Institute

Thermo Scientific 8:40-8:45 Welcome Remarks from Executive Sponsor

Scott Keefer, MBA, Manager, Product Management, Thermo Scientific High Content Products

8:45-9:45 Opening Panel Discussion



 Tenth Anniversary of HCA: Progress Report 

Hear an update from participants of the Inaugural HCA meeting 10 years ago, including recent developments in technology and applications, as well as remaining unmet needs and future directions.

Chairperson: Anthony M. Davies, Ph.D., Director, Irish National Center for High-Content Screening and Analysis (INCHA)

Panelists:

Paul A. Johnston, Ph.D., Research Associate Professor, Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh

Jonathan A. Lee, Ph.D., Senior Research Advisor, Quantitative Biology, Eli Lilly & Co.

Joe Trask, Ph.D., Head, Cellular Imaging Core, The Hamner Institutes for Health Sciences

ThermoScientific9:45-10:45 Coffee Break in the Exhibit Hall with Poster Viewing

 


High-Content Image and Data Analysis 

10:45-10:50 Chairperson's Opening Remarks

Evan F. Cromwell, Ph.D., Director, Research, Molecular Devices

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.

GE Healthcare Logo12:05 -12:20 Complex Challenges in the Field of Cellular Level Research Require NEW Paths in Your Road to Discovery

Robert Graves, Ph.D., Senior Application Specialist, GE HealthcareFor 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.
 

12:20-1:45 Enjoy Lunch on Your Own 



Image Analysis Technology Showcase 

Molecular Devices1:45-2:15 New Developments in Accelerating 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.

GeneData logo 2:15-2:45 Get the Big Picture in Phenotypic Screening for Drug Discovery

Oliver Leven, Head, Professional Services, GenedataHigh 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.

De Novo Software2:45-3:15 Analysis and Reporting for High-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.

Thermo Scientific large logo3:15-4:15 Refreshment Break in the Exhibit Hall with Poster Viewing



High-Content Image and Data Analysis (continued) 

Chairperson's Remarks

Karol Kozak, Ph.D., Head, Data Handling Unit & High-Content Screening, ETH Zurich

4:15-4:40 Using New Cell Dyes and Automated Image Processing to Evaluate Cellular Responses to Small Molecules

David W. Andrews, Ph.D., Director and Senior Scientist, Biological Sciences, Sunnybrook Research Institute, Toronto; Professor, Biochemistry, University of Toronto

Here we describe a simple approach to quantify the responses in adherent cells to small molecules based on multivariate analysis of cells stained with new mix and read dyes.  These dyes are non-toxic, non-fluorescent in water and available in several emission/excitation wavelengths compatible with existing HCA instruments. We compare multivariate analysis and clustering with more traditional measures of analysis and find that it provides high Z' sensitivity and specificity resulting in improved classification in screening.

4:40-5:05 A Label-Free Random Cell Motility Assay Based on Image Correlation Spectroscopy

Michael Prummer, Ph.D., Scientist, High-Content Screening, F. Hoffmann-La Roche AG

Cell migration is central to embryonic development, wound healing, inflammation, and cancer. Sparse metastatic cells or T-cells show isotropic and random motion, which is difficult to characterize with classical tools like scratch assays. We use image correlation spectroscopy (ICS) to quantify the speed and mode of random cell motility without labeling, identification or trajectory reconstruction. ICS offers a toolbox to analyze free, directed, hindered, or confined random walks. The random motility (RAMOT) assay is validated using THP1 immune cells, cytoskeleton modulators and Monte-Carlo simulations. Combining ICS and HCS, the RAMOT assay opens up new routes in label-free image-based drug discovery.

5:05-5:30 Image Analysis and Modeling of Cardiomyocyte Hypertrophy

Jeffrey Saucerman, Ph.D., Assistant Professor, Biomedical Engineering, University of Virginia

Cardiomyocyte hypertrophy plays a key role in the transition to heart failure. We are developing automated microscopy and image analyses to quantify the hypertrophy dynamics of individual live primary cardiomyocytes. I will present two applications. In the first, we characterized the kinetics of myocyte hypertrophy in response to transient receptor agonists. In the second example we used automated imaging to validate model predictions about the quantitative role of 11 parallel hypertrophy pathways.

5:30-5:55 An Evolving View of Cancer: High-Content Analysis and Mathematical Modeling to Study Cancer Cell Heterogeneity and Resistance

Arijit Chakravarty, Ph.D., Senior Scientist, Modeling and Simulation, DMPK, Millenium Pharmaceuticals

The changing picture of the landscape of carcinogenesis and tumor response to therapy frames cancer as a disease of genomic instability and somatic Darwinian evolution. Developing realistic model systems and methodologies to study heterogeneity and evolution in populations of cancer cells would be the first step in leveraging the emerging picture of cancer in oncology drug development. In this presentation I will discuss the challenges posed by tumor heterogeneity and evolution, and the methods by which high-content analysis techniques, coupled with mathematical modeling, allow us to study this process.

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

Thermo Scientific 11:40-11:55 New CCD Camera Technology for 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 high-content analysis and comparing it to current technologies being used in the  high-content space.

Thermo Scientific 11:55-12:10 pm Enabling High-Throughput HCS with the Cell InsightMarie Zhang, Ph.D., Co-Founder & COO, MicroStem, Inc.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.

GE Healthcare Logo12:10-12:25 New Developments in High Content Imaging Systems for Faster and More Efficient Screening

HaiGuang Zhang, Ph.D., Senior Application Consultant, GE HealthcareRapid 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.

12:25-1:45 Enjoy Lunch on Your Own



HCA for Toxicity Assessment 

Chairperson's Remarks

Paul A. Johnston, Ph.D., Research Associate Professor, Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh

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.

GE Healthcare Logo3:00-3:15 Cardiotoxicity of Oncology Drugs: High Content Analysis of Kinase Inhibitors in a Human Stem Cell Derived Cardiomyocyte Model

Nick Thomas, Ph.D., Principal Scientist, Cell Technologies, GE HealthcareIndustrial 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.
 

Thermo Scientific large logo3:15-4:15 Refreshment Break in the Exhibit Hall with Poster Viewing 



Novel Biosensor Assays for Screening 

4:15-4:40 Development, Optimization and Validation of an HCS Biosensor Assay to Identify Compounds that Disrupt AR-TIF2 Protein-Protein Interactions

Paul A. Johnston, Ph.D., Research Associate Professor, Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh

High Transcriptional Initiation Factor 2 (TIF2) coactivator expression levels are associated with prostate cancer (CaP) recurrence after androgen ablation therapy (AAT). We will describe the development and optimization of a novel high-content image-based AR-TIF2 protein-protein interaction biosensor (PPIB) assay that exploits features of protein targeting to organelles, AR and TIF2 functional domains, and fluorescent reporters to generate positional biosensors to measure and quantify the interactions between AR and TIF2 in cells. We will validate the performance of the AR-TIF2 PPI HCS assay by screening the LOPAC and NIH Clinical Collection compound libraries in two distinct formats; to identify compounds that can either block the formation or that can disrupt established AR-TIF2 PPI complexes.

4:40-5:05 Novel Approaches to High-Content Imaging of Insulin Receptor Trafficking, Insulin Signaling and Endosomal Calcium Signaling

James Johnson, Ph.D., Associate Professor, Cellular and Physiological Sciences, University of British Columbia

We have generated insulin receptor reporters that do not impair signaling function in cells and will present data on insulin receptor trafficking and signaling in pancreatic beta-cells. We have developed the first calcium biosensor capable of measuring calcium in the lumen on the endosome and will present our analysis of the role for endosomes as dynamic calcium buffers. We present multiplexing approaches to generating rich data sets reporting on insulin signaling.

5:05-5:30 High-Content Screening for Small Molecule Inhibitors of HIV Nef

Andreas Vogt, Ph.D., Associate Professor, Drug Discovery Institute, University of Pittsburgh

The HIV-1 accessory protein Nef is essential for high-titer viral replication and AIDS progression. The cellular activities of Nef are critically dependent on a variety of protein-protein interactions, including formation of Nef oligomers. Nef mutations that interfere with oligomerization prevent HIV replication in cell culture, suggesting that the Nef oligomerization interface is a rational target for Nef-directed anti-HIV therapy. In this talk, I will present the development and validation of a high-content, bimolecular fluorescence complementation assay for Nef dimerization inhibitors.


HCS at NCATS 

5:30-5:55 Supporting Drug Discovery and Reposition in NCATS Using HCS Technology

Zhuyin (Julie) Li, Ph.D., Biology Team Leader, Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, NIH

The mission of the newly created National Center for Advancing Translational Sciences (NCATS) in NIH is to catalyze the generation of innovation methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. This presentation will highlight successful applications of HCS in target validation, compound screening, MOA study, toxicity investigation and drug repositions in NCATS.

 

Thermo Scientific large logo6:00-7:00 Networking Reception in the Exhibit Hall with Poster Viewing



Advanced CourseUser Group Meetings | Main Program Wednesday | Main Program Thursday
Live-Cell Imaging Workshop | Download PDF 

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