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Multidimensional Drug Profiling By Automated Microscopy

Multidimensional Drug Profiling By Automated Microscopy. Zachary E. Perlman et al. Published 2004. Joseph Martinez and Ginger Yang. Stages of Pharmaceutical Development. Activity on Target. Off Target Activity. Effective Concentration. Use of Automated Microscopy.

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Multidimensional Drug Profiling By Automated Microscopy

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  1. Multidimensional Drug ProfilingBy Automated Microscopy Zachary E. Perlman et al. Published 2004 Joseph Martinez and Ginger Yang

  2. Stages of Pharmaceutical Development Activity on Target Off Target Activity Effective Concentration

  3. Use of Automated Microscopy • Limited throughput with current (2004) transcriptional and proteomic profiling • Automate for efficiency and cost effectiveness • Multiplex markers to screen multiple pathways and mechanisms of action • Enhanced efficiency allows concentration dose dependent analyses

  4. Experimental Setup 100 Drugs 1 Toxin (Didemnin B) 6 Alternate Titrations 3 Unknown 90 Known

  5. Testing Scheme Image and Measure Descriptors HeLa Cells in 384 Wells Treat With Drug Titrations 11 Probes

  6. Sample Image Perlman et al (2004)

  7. Quantification of Population Responses Perlman et al (2004)

  8. Comparison of Compound Profiles • Generate a Kolmogorov-Smirnov (KS) Statistic • Compute a z score by dividing KS statistic by a measure of variability in control populations • Create Heat Plot • Determine Primary Effective Concentration (PEC)

  9. Heat Maps

  10. Conclusion • Cytometric dose-response profiling successful at determining drug response profiles quantitatively • The method is fast, cheap, and unbiased. • Future work: has been commercialized today • Questions?

  11. Titration-Invariant Similarity Score (TISS)

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