Phi-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

作者：Guyon Laurent^*; Lajaunie Christian; Fer Frederic; Bhajun Ricky; Sulpice Eric; Pinna Guillaume; Campalans Anna; Radicella J Pablo; Rouillier Philippe; Mary Melissa; Combe Stephanie; Obeid Patricia; Vert Jean Philippe; Gidrol Xavier

来源：Scientific Reports, 2015, 5(1): 14221.

DOI：10.1038/srep14221

Phenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Phi-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Phi-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Phi-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Phi-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection.

• 出版日期2015-9-18
• 单位Mines Paristech; 中国地震局