[en] Network reconstruction, i.e. obtaining network structure from input-output information, is a central theme in systems biology. A variety of approaches aim to obtaining structural information from available data. Previous work has introduced dynamical structure functions as a tool for posing and solving the network reconstruction problem. Even for linear time invariant systems, reconstruction requires specific additional information not generated in the typical system identification process. This paper demonstrates that such extra information can be obtained through a limited sequence of system identification experiments on structurally modified systems, analogous to gene silencing and overexpression experiments. In the absence of such extra information, we discuss whether combined assumptions of network sparsity and minimality contribute to the recovery of the network dynamical structure. We provide sufficient conditions for a transfer function to have a completely decoupled minimal realization, and demonstrate that every transfer function is arbitrarily close to one that admits a perfectly decoupled minimal realization. This indicates that the assumptions of sparsity and minimality alone do not lend insight into the network structure.
Disciplines :
Ingénierie, informatique & technologie: Multidisciplinaire, généralités & autres
Auteur, co-auteur :
Howes, R.
Eccleston, L. J.
GONCALVES, Jorge ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Stan, G. B. V.
Warnick, S.
Langue du document :
Anglais
Titre :
Dynamical structure analysis of sparsity and minimality heuristics for reconstruction of biochemical networks
Date de publication/diffusion :
2008
Nom de la manifestation :
47th IEEE Conference on Decision and Control
Lieu de la manifestation :
Cancun, Mexique
Date de la manifestation :
December 9-11, 2008
Titre de l'ouvrage principal :
The proceedings of the 47th IEEE Conference on Decision and Control
E. Sontag, A. Kiyatkin, B. Kholodenko, "Inferring dynamic architecture of cellular networks using time series of gene expression, protein and metabolite data," IEEE Bioinformatics, Vol. 20, Issue 12, pp. 1877-1886, 2004.
N. Soranzo, G. Bianconi, C. Altafini, "Comparing association network algorithms for reverse engineering of large-scale gene regulatory networks: synthetic versus real data," Bioinformatics Vol. 23, Issue 13, pp. 1640-1647, 2007.
N. Barker, C. Myers, H. Kuwahara, "Learning Genetic Regulatory Network Connectivity from Time Series Data," Advances in Applied Artificial Intelligence, Lecture Notes in Computer Science, Vol. 4031, pp. 962-971, 2006.
N. Friedman. "Inferring Cellular Networks Using Probabilistic Graphical Models," Science, Vol. 303, Issue 5659, pp. 799-805, 2004.
K. Basso, A. A. Margolin, G. Stolovitzky, U. Klein, R. Dalla-Favera, "Reverse engineering of regulatory networks in human B cells," Nature Genetics, Vol. 37, pp. 382-390, 2005.
A. Papachristodoulou, B. Recht, "Determining Interconnections in Chemical Reaction Networks," Proceedings of the 2007 American Control Conference, pp. 4872-4877, 2007.
M. Bansal, V. Belcastro, A. Ambesi-Impiombato, and D. Di Bernardo, "How to infer gene networks from expression profiles," Molecular Systems Biology Vol. 3, Issue 78, 2007.
J. Goncalves, R. Howes, S. Warnick, "Dynamical Structure Functions for the Reverse Engineering of LTI Networks," Proceedings of the 2007 Conference on Decision and Control, pp. 1516-1522, 2007.
J. Goncalves, S. Warnick. "Necessary and Sufficient Conditions for Dynamical Structure Reconstruction of LTI Networks", IEEE Transactions of Automatic Control, 2008 (to appear).
E. Sontag, "Network reconstruction based on steady-state data". Essays in Biochemistry, 45, 2008 (to appear).
C. T. Chen, Linear System Theory and Design, Revised. Saunders College Publishing, Orlando, 1984.
D. Di Bernardo, T. Gardner, J. Collins, "Robust Identification of large genetic networks," Pac. Symp. Biocomput, Vol. 9, pp. 486-497, 2004.
B. Bamieh, L. Giarré, "On Discovering Low Order Models in Biochemical Reaction Kinetics," Proceedings of the 2007 American Control Conference, pp. 2702-2707, 2007.