title: Systematic epistatic mapping of cellular processes.
abstract: Genetic screens have identified many novel components of various biological processes, such as components required for cell cycle and cell division. While forward genetic screens typically generate unstructured 'hit' lists, genetic interaction mapping approaches can identify functional relations in a systematic fashion. Here, we discuss a recent study by our group demonstrating a two-step approach to first screen for regulators of the mitotic cell cycle, and subsequently guide hypothesis generation by using genetic interaction analysis. The screen used a high-content microscopy assay and automated image analysis to capture defects during mitotic progression and cytokinesis. Genetic interaction networks derived from process-specific features generate a snapshot of functional gene relations in those processes, which follow a temporal order during the cell cycle. This complements a recently published approach, which inferred directional genetic interactions reconstructing hierarchical relationships between genes across different phases during mitotic progression. In conclusion, this strategy leverages unbiased, genome-wide, yet highly sensitive and process-focused functional screening in cells.
authors.affiliation: German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Heidelberg University, Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany ; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union St SE, Minneapolis, MN 55455 USA.
authors.forename: Maximilian
authors.identifier: 0000-0002-6556-9594
authors.initials: M
authors.lastname: Billmann
authors.affiliation: German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Heidelberg University, Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany ; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
authors.forename: Michael
authors.identifier: 0000-0002-9458-817X
authors.initials: M
authors.lastname: Boutros
keywords: Cell cycle; Genetic interactions; Image analysis; RNAi