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PNAS 105 (6): 1913-1918

Copyright © 2008 by the National Academy of Sciences.


Emergent decision-making in biological signal transduction networks

Tomás Helikar*, John Konvalina{dagger}, Jack Heidel{dagger}, and Jim A. Rogers*,{dagger},{ddagger}

*Department of Pathology and Microbiology, University of Nebraska Medical Center, 983135 Nebraska Medical Center, Omaha, NE 68198; and {dagger}Department of Mathematics, University of Nebraska, 6001 Dodge Street, Omaha, NE 68182

Edited by Eugene V. Koonin, National Institutes of Health, Bethesda, MD, and accepted by the Editorial Board December 14, 2007

Received for publication May 30, 2007.

Abstract: The complexity of biochemical intracellular signal transduction networks has led to speculation that the high degree of interconnectivity that exists in these networks transforms them into an information processing network. To test this hypothesis directly, a large scale model was created with the logical mechanism of each node described completely to allow simulation and dynamical analysis. Exposing the network to tens of thousands of random combinations of inputs and analyzing the combined dynamics of multiple outputs revealed a robust system capable of clustering widely varying input combinations into equivalence classes of biologically relevant cellular responses. This capability was nontrivial in that the network performed sharp, nonfuzzy classifications even in the face of added noise, a hallmark of real-world decision-making.

Key Words: information processing • systems biology

Author contributions: J.K., J.H., and J.A.R. designed research; T.H., J.K., and J.A.R. performed research; T.H., J.K., and J.A.R. contributed new reagents/analytic tools; T.H., J.K., and J.A.R. analyzed data; and J.A.R. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. E.V.K. is a guest editor invited by the Editorial Board.

This article contains supporting information online at

{ddagger}To whom correspondence should be addressed. E-mail: jrogers{at}

© 2008 by The National Academy of Sciences of the USA

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