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Mathematical Biosciences and Engineering (MBE)
 

Parameter space exploration within dynamic simulations of signaling networks

Pages: 103 - 120, Volume 10, Issue 1, February 2013      doi:10.3934/mbe.2013.10.103

 
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Cristina De Ambrosi - DIBRIS Department of Informatics, Bioengineering, Robotics and Systems Engineering, Università degli Studi di Genova - Via Balbi, 5 - 16126 Genova, Italy (email)
Annalisa Barla - DIBRIS Department of Informatics, Bioengineering, Robotics and Systems Engineering, Università degli Studi di Genova - Via Balbi, 5 - 16126 Genova, Italy (email)
Lorenzo Tortolina - DIBRIS Department of Informatics, Bioengineering, Robotics and Systems Engineering, Università degli Studi di Genova - Via Balbi, 5 - 16126 Genova, Italy (email)
Nicoletta Castagnino - DIBRIS Department of Informatics, Bioengineering, Robotics and Systems Engineering, Università degli Studi di Genova - Via Balbi, 5 - 16126 Genov, Italy (email)
Raffaele Pesenti - DiMa - Department of Management, Università Ca' Foscari - Dorsoduro 3246 - 30123 Venezia, Italy (email)
Alessandro Verri - DIBRIS Department of Informatics, Bioengineering, Robotics and Systems Engineering, Università degli Studi di Genova - Via Balbi, 5 - 16126 Genova, Italy (email)
Alberto Ballestrero - Di.M.I - Department of Internal Medicine, A.O.U. IRCCS San Martino IST, Italy (email)
Franco Patrone - Di.M.I - Department of Internal Medicine, A.O.U. IRCCS San Martino IST, Italy (email)
Silvio Parodi - Di.M.I - Department of Internal Medicine, A.O.U. IRCCS San Martino IST, Italy (email)

Abstract: We started offering an introduction to very basic aspects of molecular biology, for the reader coming from computer sciences, information technology, mathematics. Similarly we offered a minimum of information about pathways and networks in graph theory, for a reader coming from the bio-medical sector. At the crossover about the two different types of expertise, we offered some definition about Systems Biology. The core of the article deals with a Molecular Interaction Map (MIM), a network of biochemical interactions involved in a small signaling-network sub-region relevant in breast cancer. We explored robustness/sensitivity to random perturbations. It turns out that our MIM is a non-isomorphic directed graph. For non physiological directions of propagation of the signal the network is quite resistant to perturbations. The opposite happens for biologically significant directions of signal propagation. In these cases we can have no signal attenuation, and even signal amplification. Signal propagation along a given pathway is highly unidirectional, with the exception of signal-feedbacks, that again have a specific biological role and significance. In conclusion, even a relatively small network like our present MIM reveals the preponderance of specific biological functions over unspecific isomorphic behaviors. This is perhaps the consequence of hundreds of millions of years of biological evolution.

Keywords:  Systems biology, Molecular Interaction Maps, signaling networks, dynamic simulations, parameter space exploration.
Mathematics Subject Classification:  Primary: 92C42; Secondary: 92C40.

Received: April 2012;      Accepted: July 2012;      Available Online: December 2012.

 References