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Analysis of the Growth Control Network Specific for Human LungAdenocarcinoma 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: [email protected]
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Abstract

Many cancer-associated genes and pathways remain to be identified in order to clarify themolecular mechanisms underlying cancer progression. In this area, genome-wideloss-of-function screens appear to be powerful biological tools, allowing the accumulationof large amounts of data. However, this approach currently lacks analytical tools toexploit the data with maximum efficiency, for which systems biology methods analyzingcomplex cellular networks may be extremely helpful. In this article we report such asystems biology strategy based on the construction of a Network for a biological processand specific for a given cell system (cell type). The networks are created fromgenome-wide loss-of-function screen datasets. We also propose tools to analyze networkproperties. As one of the tools, we suggest a mathematical model for discriminationbetween two distinct cell processes that may be affected by knocking down the activity ofa gene, i. e., a decreased cell number may be caused by arrested cell proliferation orenhanced cell death. Next we show how this discrimination between the two cell processeshelps to construct two corresponding subnetworks. Finally, we demonstrate an applicationof the proposed strategy to the identification and characterization of putative novelgenes and pathways significant for the control of lung cancer cell growth, based on theresults of a genome-wide proliferation/viability loss-of-function screen of human lungadenocarcinoma 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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