INTEGRATIVE APPROACHES TO MOLECULAR BIOLOGY

By J. JOLID

Part I Introduction to High Content Screening 1 Past, Present, and Future of High Content Screening and the Field of Cellomics 2 A Pharmaceutical Company User’s Perspective on the Potential of High Content Screening in Drug Discovery 3 Linking Microscopy and High Content Screening in Large-Scale Biomedical Research Part II Instrumentation, Biological Application Software, and Sample Preparation 4 Requirements, Features, and Performance of High Content Screening Platforms 5 Characteristics and Value of Directed Algorithms in High Content Screening 6 Characteristics and Value of Machine Learning for Imaging in High Content Screening 7 Tools for Quantitative and Validated Measurements of Cells 8 Automated Cell Plating and Sample Treatments for Fixed Cells in High Content Assays 9 Differentiating Primary Human Cells in Rapid-Throughput Discovery Applications 10 Use of the CellCard™ System for Analyzing Multiple Cell Types in Parallel 3 19 33 41 63 83 95 109 121 129 Part III Reagents 11 Reagents to Measure and Manipulate Cell Functions 12 Fluorescent Proteins and Engineered Cell Lines 13 Optimizing the Integration of Immunoreagents and Fluorescent Probes for Multiplexed High Content Screening Assays 14 The HaloTag™: A Novel Technology for Cell Imaging and Protein Analysis 15 Protein Labeling With FlAsH and ReAsH 16 Exploiting Network Biology to Improve Drug Discovery 17 Physiological Indicators of Cell Function 18 The Use of siRNA to Validate Immunofluorescence Studies 19 Caged Substrates Applied to High Content Screening: An Introduction With an Eye to the Future Part IV Informatics and Bioinformatics 20 Overview of Informatics for High Content Screening 21 Large-Scale Data Management for High Content Screening 22 An Integrated Biomedical Knowledge Extraction and Analysis Platform: Using Federated Search and Document Clustering Technology 23 Visualization of High Content Screening Data 24 Pathway Mapping Tools for Analysis of High Content Data 141 165 189 195 209 221 233 245 253 269 281 293 301 319 Part V Assays and Applications of High Content Screening 25 Systems Biology in Cancer Research: Genomics to Cellomics 26 Target Validation in Drug Discovery 27 High Content Screening as a Screening Tool in Drug Discovery 28 Discovery of Protein Kinase Phosphatase Inhibitors 29 High Content Translocation Assays for Pathway Profiling 30 In Vitro Cytotoxicity Assessment 31 Neurite Outgrowth in Retinal Ganglion Cell Culture 353 367 379 389 401 415 427