Jan Ellenberg及其同事利用RNA干涉来将一个人类细胞系中大约21,000个蛋白编码基因中的每个基因沉默，然后利用对活的、正在分裂的细胞进行高通过量时间延迟成像的方法来记录结果。
通过对每个基因至少6个时长为两天的影片进行计算机图像处理，来对表现型进行量化打分。数百个基因被发现在有丝分裂和包括细胞存活及迁移在内的其他细胞过程中发挥功能。
该研究的整个数据集作为一个公共功能基因组资源发布在ｗｗｗ.ｍｉｔｏｃｈｅｃｋ.ｏｒｇ网站上。(生物谷Bioon.com)
生物谷推荐原文出处：
Nature doi:10.1038/nature08869
Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes
Beate Neumann1,12, Thomas Walter1,12, Jean-Karim Hériché5,13, Jutta Bulkescher1, Holger Erfle1,3,13, Christian Conrad1,3, Phill Rogers1,13, Ina Poser6, Michael Held1,13, Urban Liebel1,13, Cihan Cetin3, Frank Sieckmann8, Gregoire Pau9, Rolf Kabbe10, Annelie Wünsche2, Venkata Satagopam4, Michael H. A. Schmitz7, Catherine Chapuis3, Daniel W. Gerlich7, Reinhard Schneider4, Roland Eils10, Wolfgang Huber9, Jan-Michael Peters11, Anthony A. Hyman6, Richard Durbin5, Rainer Pepperkok3 & Jan Ellenberg2
MitoCheck Project Group,
Gene Expression and,
Cell Biology/Biophysics Units, Structural and,
Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany
Institute of Biochemistry, Swiss Federal Institute of Technology Zurich (ETHZ), Schafmattstrasse 18, CH-8093 Zurich, Switzerland
Leica Microsystems CMS GmbH, Am Friedensplatz 3, D-68165 Mannheim, Germany
European Bioinformatics Institute, European Molecular Biology Laboratory, Cambridge CB10 1SD, UK
Division of Theoretical Bioinformatics, German Cancer Research Center, Im Neuenheimer Feld 267, D-69120 Heidelberg, Germany
Institute for Molecular Pathology, Dr Bohr Gasse 7, A-1030 Vienna, Austria
These authors contributed equally to this work.
Present addresses: MitoCheck Project Group, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany (J.-K.H.); BIOQUANT Centre University Heidelberg, INF 267, D-69120 Heidelberg, Germany (H.E.); 3-V Biosciences GmbH, Wagistrasse 27, 8952 Schlieren, Switzerland (P.R.); Institute of Biochemistry, Swiss Federal Institute of Technology Zurich (ETHZ), Schafmattstrasse 18, CH-8093 Zurich, Switzerland (M.H.); Karlsruhe Institute of Technology KIT, Herrmann-von-Helmholtz Platz 1, D-76344 Eggenstein-Leopoldshafen, Germany (U.L.).
Despite our rapidly growing knowledge about the human genome, we do not know all of the genes required for some of the most basic functions of life. To start to fill this gap we developed a high-throughput phenotypic screening platform combining potent gene silencing by RNA interference, time-lapse microscopy and computational image processing. We carried out a genome-wide phenotypic profiling of each of the ~21,000 human protein-coding genes by two-day live imaging of fluorescently labelled chromosomes. Phenotypes were scored quantitatively by computational image processing, which allowed us to identify hundreds of human genes involved in diverse biological functions including cell division, migration and survival. As part of the Mitocheck consortium, this study provides an in-depth analysis of cell division phenotypes and makes the entire high-content data set available as a resource to the community.
