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Analysis of the Growth Control Network Specific for Human Lung Adenocarcinoma Cells

Published online by Cambridge University Press:  25 January 2012

G. Pinna ,
A. Zinovyev ,
N. Araujo ,
N. Morozova  and
A. Harel-Bellan
G. Pinna
Affiliation:
CNRS FRE 3377, CEA Saclay, Gif-sur-Yvette, F-91191 and Universite Paris-Sud, Gif-sur-Yvette, F-91191, France
A. Zinovyev
Affiliation:
Institut Curie, 26 rue d’Ulm, Paris, France INSERM, U900, F-75248 Paris, France Mines ParisTech, Centre for Computational Biology, F-77300 Fontainebleau, France
N. Araujo
Affiliation:
CNRS FRE 3377, CEA Saclay, Gif-sur-Yvette, F-91191 and Universite Paris-Sud, Gif-sur-Yvette, F-91191, France
N. Morozova*
Affiliation:
CNRS FRE 3377, CEA Saclay, Gif-sur-Yvette, F-91191 and Universite Paris-Sud, Gif-sur-Yvette, F-91191, France
A. Harel-Bellan
Affiliation:
CNRS FRE 3377, CEA Saclay, Gif-sur-Yvette, F-91191 and Universite Paris-Sud, Gif-sur-Yvette, F-91191, France
*
⋆ Corresponding author. E-mail: morozova@vjf.cnrs.fr
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Abstract

Many cancer-associated genes and pathways remain to be identified in order to clarify the molecular mechanisms underlying cancer progression. In this area, genome-wide loss-of-function screens appear to be powerful biological tools, allowing the accumulation of large amounts of data. However, this approach currently lacks analytical tools to exploit the data with maximum efficiency, for which systems biology methods analyzing complex cellular networks may be extremely helpful. In this article we report such a systems biology strategy based on the construction of a Network for a biological process and specific for a given cell system (cell type). The networks are created from genome-wide loss-of-function screen datasets. We also propose tools to analyze network properties. As one of the tools, we suggest a mathematical model for discrimination between two distinct cell processes that may be affected by knocking down the activity of a gene, i. e., a decreased cell number may be caused by arrested cell proliferation or enhanced cell death. Next we show how this discrimination between the two cell processes helps to construct two corresponding subnetworks. Finally, we demonstrate an application of the proposed strategy to the identification and characterization of putative novel genes and pathways significant for the control of lung cancer cell growth, based on the results of a genome-wide proliferation/viability loss-of-function screen of human lung adenocarcinoma cells.

Keywords

systems biologynetwork analysislung adenocarcinomagenome-wide screen
Type
Research Article
Information
Mathematical Modelling of Natural Phenomena , Volume 7 , Issue 1: Cancer modeling , 2012 , pp. 337 - 368
Copyright
© EDP Sciences, 2012

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