The next step in systems biology: simulating the temporospatial dynamics of molecular network.

As a result of the time- and context-dependency of gene expression, gene regulatory and signaling pathways undergo dynamic changes during development. Creating a model of the dynamics of molecular interaction networks offers enormous potential for understanding how a genome orchestrates the developmental processes of an organism. The dynamic nature of pathway topology calls for new modeling strategies that can capture transient molecular links at the runtime. The aim of this paper is to present a brief and informative, but not all-inclusive, viewpoint on the computational aspects of modeling and simulation of a non-static molecular network.

[1]  M. Tomita.  Whole-cell simulation: a grand challenge of the 21st century. , 2001, Trends in biotechnology.

[2]  K. Sneppen,et al.  Specificity and Stability in Topology of Protein Networks , 2002, Science.

[3]  K. Kohn.  Molecular interaction map of the mammalian cell cycle control and DNA repair systems. , 1999, Molecular biology of the cell.

[4]  P. Nurse,et al.  Reductionism: The ends of understanding , 1997, Nature.

[5]  J. Marks,et al.  A SAGE (serial analysis of gene expression) view of breast tumor progression. , 2001, Cancer research.

[6]  H. Kitano,et al.  Computational systems biology , 2002, Nature.

[7]  S. Gray,et al.  Possible interactions between angiotensin II and insulin: effects on glucose and lipid metabolism in vivo and in vitro. , 2000, The Journal of endocrinology.

[8]  R. Albert,et al.  The large-scale organization of metabolic networks , 2000, Nature.

[9]  Tandy J. Warnow,et al.  Toward new software for computational phylogenetics , 2002, Computer.

[10]  S. Huang,et al.  Genomics, complexity and drug discovery: insights from Boolean network models of cellular regulation. , 2001, Pharmacogenomics.

[11]  L. Loew,et al.  The Virtual Cell: a software environment for computational cell biology. , 2001, Trends in biotechnology.

[12]  Benno Schwikowski,et al.  Discovering regulatory and signalling circuits in molecular interaction networks , 2002, ISMB.

[13]  Marc Vidal,et al.  Yeast Two-hybrid Systems and Protein Interaction Mapping Projects for Yeast and Worm , 2022 .

[14]  S. Schuster,et al.  Metabolic network structure determines key aspects of functionality and regulation , 2002, Nature.

[15]  H. Hirata,et al.  Oscillatory Expression of the bHLH Factor Hes1 Regulated by a Negative Feedback Loop , 2002, Science.

[16]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Kurt W Kohn,et al.  Functional capabilities of molecular network components controlling the mammalian G1/S cell cycle phase transition , 1998, Oncogene.

[18]  A. Magliocco,et al.  A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors , 2003, Cancer.

[19]  A. Barabasi,et al.  Hierarchical Organization of Modularity in Metabolic Networks , 2002, Science.

[20]  B. Ursø,et al.  Role of the time factor in signaling specificity: application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-I receptor tyrosine kinases. , 1995, Metabolism: clinical and experimental.

[21]  Robert W. Sebesta,et al.  Concepts of programming languages , 1973 .

[22]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

[23]  Tamas Vicsek.  Complexity: The bigger picture , 2002, Nature.

[24]  Sui Huang,et al.  The practical problems of post-genomic biology , 2000, Nature Biotechnology.