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Time-Resolved Human Kinome RNAi Screen Identifies a Network Regulating Mitotic-Events as Early Regulators of Cell Proliferation.
MedLine Citation:
PMID:  21765947     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Analysis of biological processes is frequently performed with the help of phenotypic assays where data is mostly acquired in single end-point analysis. Alternative phenotypic profiling techniques are desired where time-series information is essential to the biological question, for instance to differentiate early and late regulators of cell proliferation in loss-of-function studies. So far there is no study addressing this question despite of high unmet interests, mostly due to the limitation of conventional end-point assaying technologies. We present the first human kinome screen with a real-time cell analysis system (RTCA) to capture dynamic RNAi phenotypes, employing time-resolved monitoring of cell proliferation via electrical impedance. RTCA allowed us to investigate the dynamics of phenotypes of cell proliferation instead of using conventional end-point analysis. By introducing data transformation with first-order derivative, i.e. the cell-index growth rate, we demonstrate this system suitable for high-throughput screenings (HTS). The screen validated previously identified inhibitor genes and, additionally, identified activators of cell proliferation. With the information of time kinetics available, we could establish a network of mitotic-event related genes to be among the first displaying inhibiting effects after RNAi knockdown. The time-resolved screen captured kinetics of cell proliferation caused by RNAi targeting human kinome, serving as a resource for researchers. Our work establishes RTCA technology as a novel robust tool with biological and pharmacological relevance amenable for high-throughput screening.
Authors:
Jitao David Zhang; Cindy Koerner; Stephanie Bechtel; Christian Bender; Ioanna Keklikoglou; Christian Schmidt; Anja Irsigler; Ute Ernst; Ozgür Sahin; Stefan Wiemann; Ulrich Tschulena
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Publication Detail:
Type:  Journal Article     Date:  2011-07-13
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-07-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e22176     Citation Subset:  IM    
Affiliation:
Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
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