A scalable and integrative system for pathway bioinformatics and systems biology.

MOTIVATION Progress in systems biology depends on developing scalable informatics tools to predictively model, visualize, and flexibly store information about complex biological systems. Scalability of these tools, as well as their ability to integrate within larger frameworks of evolving tools, is critical to address the multi-scale and size complexity of biological systems. RESULTS Using current software technology, such as self-generation of database and object code from UML schemas, facilitates rapid updating of a scalable expert assistance system for modeling biological pathways. Distribution of key components along with connectivity to external data sources and analysis tools is achieved via a web service interface. AVAILABILITY All sigmoid modeling software components and supplementary information are available through: http://www.igb.uci.edu/servers/sb.html.

[1]  Pierre Baldi,et al.  Sigmoid: a software infrastructure for pathway bioinformatics and systems biology , 2005, IEEE Intelligent Systems.

[2]  A. Hoffmann,et al.  The I (cid:1) B –NF-(cid:1) B Signaling Module: Temporal Control and Selective Gene Activation , 2022 .

[3]  Bruce E. Shapiro,et al.  An enzyme mechanism language for the mathematical modeling of metabolic pathways , 2005, Bioinform..

[4]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[5]  D. Fell,et al.  Applications of metabolic modelling to plant metabolism. , 2004, Journal of experimental botany.

[6]  A. Hoffmann,et al.  The IkappaB-NF-kappaB signaling module: temporal control and selective gene activation. , 2002, Science.

[7]  G. W. Hatfield,et al.  A Mathematical Model for the Branched Chain Amino Acid Biosynthetic Pathways of Escherichia coli K12* , 2005, Journal of Biological Chemistry.

[8]  Andre Levchenko,et al.  GSK-3 kinases enhance calcineurin signaling by phosphorylation of RCNs. , 2004, Genes & development.

[9]  J. Tyson,et al.  A simple model of circadian rhythms based on dimerization and proteolysis of PER and TIM. , 1999, Biophysical journal.

[10]  Eric Mjolsness,et al.  Dynamic biological signaling pathway modeling and parameter estimation through optimization , 2008 .

[11]  Bruce E. Shapiro,et al.  Cellerator: extending a computer algebra system to include biochemical arrows for signal transduction simulations , 2003, Bioinform..

[12]  I. H. Segel.  Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems , 1975 .

[13]  William Stein,et al.  SAGE: Software for Algebra and Geometry Experimentation , 2006 .

[14]  B. Kholodenko,et al.  Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades. , 2000, European journal of biochemistry.

[15]  B. Kholodenko,et al.  Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades , 2004, The Journal of cell biology.

[16]  H. Busse,et al.  Sustained oscillations in glycolysis: an experimental and theoretical study of chaotic and complex periodic behavior and of quenching of simple oscillations. , 1998, Biophysical chemistry.

[17]  B. Kholodenko,et al.  Quantification of Short Term Signaling by the Epidermal Growth Factor Receptor* , 1999, The Journal of Biological Chemistry.

[18]  Edda Klipp,et al.  Modelling the dynamics of the yeast pheromone pathway , 2004, Yeast.

[19]  Pierre Baldi,et al.  Retroviruses and yeast retrotransposons use overlapping sets of host genes. , 2005, Genome research.

[20]  A Goldbeter,et al.  Complex intracellular calcium oscillations. A theoretical exploration of possible mechanisms. , 1997, Biophysical chemistry.

[21]  Wolfgang Marwan,et al.  Theory of time-resolved somatic complementation and its use to explore the sporulation control network in Physarum polycephalum. , 2003, Genetics.

[22]  M. V. van Boekel,et al.  Kinetic modeling of reactions in heated monosaccharide-casein systems. , 2002, Journal of agricultural and food chemistry.

[23]  A. Fersht,et al.  Rescuing the function of mutant p53 , 2001, Nature Reviews Cancer.

[24]  Jean-Marc Delosme,et al.  Performance of a new annealing schedule , 1988, 25th ACM/IEEE, Design Automation Conference.Proceedings 1988..

[25]  H. Gutfreund,et al.  Enzyme kinetics , 1975, Nature.

[26]  J E Ferrell,et al.  The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. , 1998, Science.

[27]  Bruce E. Shapiro,et al.  Application of a Generalized Mwc Model for the Mathematical Simulation of Metabolic Pathways Regulated by Allosteric Enzymes , 2006, J. Bioinform. Comput. Biol..