Background: Despite decades of new discoveries in biomedical research, the overwhelming complexity of cells has been a significant barrier to a fundamental understanding of how cells work as a whole. As such, the holistic study of biochemical pathways requires computer modeling. Due to the complexity of cells, it is not feasible for one person or group to model the cell in its entirety. Results:The Cell Collective is a platform that allows the world-wide scientific community to create these models collectively. Its interface enables users to build and use models without specifying any mathematical equations or computer code -addressing one of the major hurdles with computational research. In addition, this platform allows scientists to simulate and analyze the models in real-time on the web, including the ability to simulate loss/gain of function and test what-if scenarios in real time. Conclusions:The Cell Collective is a web-based platform that enables laboratory scientists from across the globe to collaboratively build large-scale models of various biological processes, and simulate/analyze them in real time. In this manuscript, we show examples of its application to a large-scale model of signal transduction.

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.information processing ͉ systems biology

This paper is an analytical study of Boolean networks. The motivation is our desire to understand the large, complicated and interconnected pathways which comprise intracellular biochemical signal transduction networks. The simplest possible conceptual model that mimics signal transduction with sigmoidal kinetics is the n-node Boolean network each of whose elements or nodes has the value 0 (off) or 1 (on) at any given time T = 0, 1, 2, …. A Boolean network has 2nstates all of which are either on periodic cycles (including fixed points) or transients leading to cycles. Thus one understands a Boolean network by determining the number and length of its cycles. The problem one must circumvent is the large number of states (2n) since the networks we are interested in have 100 or more elements. Thus we concentrate on developing size n methods rather than the impossible task of enumerating all 2nstates. This is done as follows: the dynamics of the network can be described by n polynomial equations which describe the logical function which determines the interaction at each node. Iterating the equations one step at a time finds all fixed points, period two cycles, period three cycles, etc. This is a general method that can be used to determine the fixed points and moderately large periodic cycles of any size network, but it is not useful in finding the largest cycles in a large network. However, we also show that the network equations can often be reduced to scalar form, which makes the cycle structure much more transparent. The scalar equations method is a true "size n" method and several examples (including nontrivial biochemical systems) are examined.

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One way of coping with the complexity of biological systems is to use the simplest possible models which are able to reproduce at least some nontrivial features of reality. Although two value Boolean models have a long history in technology, it is perhaps a little bit surprising that they can also represent important features of living organizms. In this paper, the scalar equation approach to Boolean network models is further developed and then applied to two interesting biological models. In particular, a linear reduced scalar equation is derived from a more rudimentary nonlinear scalar equation. This simpler, but higher order, two term equation gives immediate information about both cycle and transient structure of the network.

STATs (signal transducers and activators of transcription) are a class of transcription factors with SH2 domains that are activated in response to tyrosine phosphorylation. STATs are often activated by members of the JAK family of protein-tyrosine kinases in response to cytokine stimulation. The activation mechanism involves SH2-dependent recruitment of the STATs to tyrosine-phosphorylated cytokine receptors. The STATs are then phosphorylated by receptor-associated JAKs, which induces dimerization via reciprocal SH2-phosphotyrosine interaction. The STAT dimers then enter the nucleus and bind specific DNA elements, leading to transcriptional activation. The JAK-STAT pathway is the subject of many