Billmann Maximilian, Boutros Michael
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.
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.
Cell Div. 2017 Jan 6;12:2. doi: 10.1186/s13008-016-0028-z. eCollection 2017.
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.
遗传筛选已鉴定出各种生物学过程的许多新成分，例如细胞周期和细胞分裂所需的成分。虽然正向遗传筛选通常会生成无结构的“命中”列表，但遗传相互作用图谱方法可以系统地识别功能关系。在这里，我们讨论了我们团队最近的一项研究，该研究展示了一种两步法，首先筛选有丝分裂细胞周期的调节因子，随后通过遗传相互作用分析来指导假设的产生。该筛选使用了高内涵显微镜检测和自动图像分析来捕捉有丝分裂进程和胞质分裂过程中的缺陷。从特定过程特征衍生的遗传相互作用网络生成了这些过程中功能基因关系的快照，这些关系在细胞周期中遵循时间顺序。这补充了最近发表的一种方法，该方法推断了有丝分裂进程中不同阶段基因之间的定向遗传相互作用，重建了层次关系。总之，该策略利用了细胞中无偏向、全基因组、高度敏感且以过程为重点的功能筛选。
