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Single-cell and multivariate approaches in genetic perturbation screens
Single-cell and multivariate approaches in genetic perturbation screens
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Single-cell and multivariate approaches in genetic perturbation screens
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Single-cell and multivariate approaches in genetic perturbation screens
Single-cell and multivariate approaches in genetic perturbation screens

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Single-cell and multivariate approaches in genetic perturbation screens
Single-cell and multivariate approaches in genetic perturbation screens
Journal Article

Single-cell and multivariate approaches in genetic perturbation screens

2015
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Overview
Key Points There are a number of different methods and techniques for genetic perturbation screens. The phenomenon of cell-to-cell variability in mammalian cells has implications for the interpretation of gene function. We now have the ability to quantify, at a large scale, multiple parameters of genetic perturbation effects in thousands of single cells. Functional genetic interactions can be inferred from multivariate quantitative readouts. We present an outlook on the opportunities that the single-cell paradigm will bring to unravel the biological complexity of mammalian cells. Large-scale genetic perturbation screens have been central to many biological discoveries. This Review outlines the recent advances in the quantification of various perturbations across large numbers of single cells simultaneously and describes the use of genetic perturbation screens to infer functional interactions between genes and phenotypes. Large-scale genetic perturbation screens are a classical approach in biology and have been crucial for many discoveries. New technologies can now provide unbiased quantification of multiple molecular and phenotypic changes across tens of thousands of individual cells from large numbers of perturbed cell populations simultaneously. In this Review, we describe how these developments have enabled the discovery of new principles of intracellular and intercellular organization, novel interpretations of genetic perturbation effects and the inference of novel functional genetic interactions. These advances now allow more accurate and comprehensive analyses of gene function in cells using genetic perturbation screens.