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Formation of Regulatory Patterns During Signal Propagation in a Mammalian Cellular Network
Avi Ma'ayan,1Sherry L. Jenkins,1Susana Neves,1Anthony Hasseldine,1Elizabeth Grace,1Benjamin Dubin-Thaler,3Narat J. Eungdamrong,1Gehzi Weng,1*Prahlad T. Ram,1J. Jeremy Rice,4Aaron Kershenbaum,4Gustavo A. Stolovitzky,4Robert D. Blitzer,1,2Ravi Iyengar1
We developed a model of 545 components (nodes) and 1259 interactionsrepresenting signaling pathways and cellular machines in thehippocampal CA1 neuron. Using graph theory methods, we analyzedligand-induced signal flow through the system. Specificationof input and output nodes allowed us to identify functionalmodules. Networking resulted in the emergence of regulatorymotifs, such as positive and negative feedback and feedforwardloops, that process information. Key regulators of plasticitywere highly connected nodes required for the formation of regulatorymotifs, indicating the potential importance of such motifs indetermining cellular choices between homeostasis and plasticity.
1 Department of Pharmacology and Biological Chemistry Mount Sinai School of Medicine, New York, NY 10029, USA. 2 Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA. 3 Department of Biological Sciences, Columbia University, New York, NY 10029, USA. 4 Functional Genomics and Systems Biology, IBM T. J. Watson Research Center, Yorktown Heights, NY 10598, USA.
* Present address: Scios Inc., 6500 Paseo Padre Parkway, Fremont,CA 94555, USA.
Present address: Department of Molecular Therapeutics, M. D.Anderson Cancer Center, Houston, TX 77025, USA.
To whom correspondence should be addressed. E-mail: Ravi.Iyengar{at}mssm.edu
Functions of Bifans in Context of Multiple Regulatory Motifs in Signaling Networks.
A. Lipshtat, S. P. Purushothaman, R. Iyengar, and A. Ma'ayan (2008)
Biophys. J.
94, 2566-2579
|Abstract »|Full Text »|PDF »
Gene expression dynamics in the macrophage exhibit criticality.
M. Nykter, N. D. Price, M. Aldana, S. A. Ramsey, S. A. Kauffman, L. E. Hood, O. Yli-Harja, and I. Shmulevich (2008)
PNAS
105, 1897-1900
|Abstract »|Full Text »|PDF »
Emergent decision-making in biological signal transduction networks.
T. Helikar, J. Konvalina, J. Heidel, and J. A. Rogers (2008)
PNAS
105, 1913-1918
|Abstract »|Full Text »|PDF »
Network Inference, Analysis, and Modeling in Systems Biology.
Present address: Department of Molecular Therapeutics, M. D. Anderson Cancer Center, Houston, TX 77025, USA. 
To whom correspondence should be addressed. E-mail: 
