Functional genomic and high-content screening for target discovery and deconvolution

Abstract

Introduction: Functional genomic screens apply knowledge gained from the sequencing of the human genome toward rapid methods of identifying genes involved in cellular function based on a specific phenotype. This approach has been made possible through advances in both molecular biology and automation. The utility of this approach has been further enhanced through the application of image-based high-content screening: an automated microscopy and quantitative image analysis platform. These approaches can significantly enhance the acquisition of novel targets for drug discovery.

Areas covered: Both the utility and potential issues associated with functional genomic screening approaches are discussed in this review, along with examples that illustrate both. The considerations for high-content screening applied to functional genomics are also presented.

Expert opinion: Functional genomic screening and high-content screening are extremely useful in the identification of new drug targets. However, the technical, experimental, and computational parameters have an enormous influence on the results. Thus, although new targets are identified, caution should be applied to the interpretation of screening data in isolation. Genomic screens should be viewed as an integral component of a target identification campaign that requires both the acquisition of orthogonal data, as well as a rigorous validation strategy.

Keywords::

• genome-wide siRNA screening
• high-content screening
• target deconvolution
• target identification

Acknowledgement

The authors would like to thank CY Chiang for his help with the manuscript. SKC was supported by grants P01 AI090935 and P50 GM085764 from the National Institutes of Health (NIH).

Notes

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