https://staging.physiomeproject.org/w/hnielsen/saez_rodriguez_2004 en-us The study of detailed models for intracellular networks has become popular in recent years. New experimental techniques provide significant amounts of data that can be used to develop detailed models of intracellular networks, including signal transduction pathways. In the simplest case, the two-component system, the signaling system consists of two elements: a sensor that detects environmental changes and a regulatory element that influences the transcription of selected genes. In higher cells, however, signal transduction networks involve components that are embedded in feedback loops and interact with each other. The number of elements involved and their complicated nonlinear interactions give rise to a picture of significant complexity. Applying system-theoretic tools to biological systems has attracted increasing interest, leading to the emergence of the field of systems biology [1]. In particular, a decomposition into smaller units or modules, as well as the subsequent analysis of the resulting elements, has been proposed as a useful tool for shedding light on the rationale of signaling networks [2]. How these modules should be defined, however, remains an open question [3]. Furthermore, thorough systems-theory-oriented analyses of signaling networks based on their modularity are still scarce. This article is organized as follows. First, we describe the mechanisms that cells have developed to process information. Second, we discuss the decomposition of signaling networks into subsystems. We then present a novel criterion for defining modules based on the absence of retroactivity [4]. Some simple criteria for the analysis of the resulting units are introduced. Finally, we apply these tools to several examples. https://staging.physiomeproject.org/w/hnielsen/saez_rodriguez_2004/@@file/a8daf3bf5f6a7964e04e5cc6a1437430d2d99417 Added HTML file Hanne Nielsen 2011-08-23 https://staging.physiomeproject.org/w/hnielsen/saez_rodriguez_2004/@@file/d76c94fcab2c471b628afeacf5d6c945e3f03efa Removed extra info from CellML file. Open Cell thinks it is not valid CellML and will not run it Hanne Nielsen 2011-08-22 https://staging.physiomeproject.org/w/hnielsen/saez_rodriguez_2004/@@file/7647ad63cf23dac34076a71a01f47e2a0e6e4cb2 Added images in ai png and svg format Hanne Nielsen 2011-04-15 https://staging.physiomeproject.org/w/hnielsen/saez_rodriguez_2004/@@file/6f6599bb03073dda1ea6d9eb47cba188e99de257 Added metadata to end of CellML file. No pub med reference. Hanne Nielsen 2011-03-04 https://staging.physiomeproject.org/w/hnielsen/saez_rodriguez_2004/@@file/4834177e4bd6b816a14df8f62b10a05b97887509 Added cellML file to workspace, does not reproduce results as missing initial conditions for psi, E0, S, n and Rp Hanne Nielsen 2011-02-28