title: Φ-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays.
abstract: 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 Φ-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Φ-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 Φ-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Φ-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.
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Guyon
authors.affiliation: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology, F-77300 Fontainebleau, France.|Institut Curie, F-75248 Paris, France.|INSERM, U900, F-75248 Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Lajaunie
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fer
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Ricky
authors.initials: R
authors.lastname: Bhajun
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Sulpice
authors.affiliation: Plateforme ARN interférence (PArI), DSV/IBITEC-S/SBIGEM/UMR 9198, CEA SACLAY, F-91191 Gif-sur-Yvette.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pinna
authors.affiliation: CEA, Institute of Molecular and Cellular Radiobiology, F-92265 Fontenay aux Roses, France.|INSERM, U967, F-92265 Fontenay-aux-Roses, France.|Université Paris Diderot, U967, F-92265 Fontenay-aux-Roses, France.|Université Paris Sud, U967, F-92265 Fontenay-aux-Roses, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Campalans
authors.affiliation: CEA, Institute of Molecular and Cellular Radiobiology, F-92265 Fontenay aux Roses, France.|INSERM, U967, F-92265 Fontenay-aux-Roses, France.|Université Paris Diderot, U967, F-92265 Fontenay-aux-Roses, France.|Université Paris Sud, U967, F-92265 Fontenay-aux-Roses, France.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Radicella
authors.affiliation: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology, F-77300 Fontainebleau, France.|Institut Curie, F-75248 Paris, France.|INSERM, U900, F-75248 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rouillier
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Mary
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Combe
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Obeid
authors.affiliation: MINES ParisTech, PSL-Research University, CBIO-Centre for Computational Biology, F-77300 Fontainebleau, France.|Institut Curie, F-75248 Paris, France.|INSERM, U900, F-75248 Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vert
authors.affiliation: Université Grenoble-Alpes, F-38000 Grenoble, France.|CEA, iRTSV, Biologie à Grande Echelle, F-38054 Grenoble, France.|INSERM, U1038, F-38054 Grenoble, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gidrol