Regulatory network reconstruction using an integral additive model with flexible kernel functions

<p>Abstract</p> <p>Background</p> <p>Reconstruction of regulatory networks is one of the most challenging tasks of systems biology. A limited amount of experimental data and little prior knowledge make the problem difficult to solve. Although models that are currently used for inferring regulatory networks are sometimes able to make useful predictions about the structures and mechanisms of molecular interactions, there is still a strong demand to develop increasingly universal and accurate approaches for network reconstruction.</p> <p>Results</p> <p>The additive regulation model is represented by a set of differential equations and is frequently used for network inference from time series data. Here we generalize this model by converting differential equations into integral equations with adjustable kernel functions. These kernel functions can be selected based on prior knowledge or defined through iterative improvement in data analysis. This makes the integral model very flexible and thus capable of covering a broad range of biological systems more adequately and specifically than previous models.</p> <p>Conclusion</p> <p>We reconstructed network structures from artificial and real experimental data using differential and integral inference models. The artificial data were simulated using mathematical models implemented in JDesigner. The real data were publicly available yeast cell cycle microarray time series. The integral model outperformed the differential one for all cases. In the integral model, we tested the zero-degree polynomial and single exponential kernels. Further improvements could be expected if the kernel were selected more specifically depending on the system.</p

Cell death and life in cancer: mathematical modeling of cell fate decisions

Tumor development is characterized by a compromised balance between cell life and death decision mechanisms, which are tighly regulated in normal cells. Understanding this process provides insights for developing new treatments for fighting with cancer. We present a study of a mathematical model describing cellular choice between survival and two alternative cell death modalities: apoptosis and necrosis. The model is implemented in discrete modeling formalism and allows to predict probabilities of having a particular cellular phenotype in response to engagement of cell death receptors. Using an original parameter sensitivity analysis developed for discrete dynamic systems, we determine the critical parameters affecting cellular fate decision variables that appear to be critical in the cellular fate decision and discuss how they are exploited by existing cancer therapies

NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps

Molecular biology knowledge can be systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist a number of maps of molecular interactions containing detailed description of various cell mechanisms. It is difficult to explore these large maps, to comment their content and to maintain them. Though there exist several tools addressing these problems individually, the scientific community still lacks an environment that combines these three capabilities together. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. NaviCell combines three features: (1) efficient map browsing based on Google Maps engine; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting the community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of their interest in the context of signaling pathways and cross-talks between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive fashion due to an imbedded blogging system. NaviCell provides an easy way to explore large-scale maps of molecular interactions, thanks to the Google Maps and WordPress interfaces, already familiar to many users. Semantic zooming used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization meaningful to the user. In addition, NaviCell provides a framework for community-based map curation.Comment: 20 pages, 5 figures, submitte