URC fuzzy modeling and simulation of gene regulation

Recent technological advances in high-throughput data collection give biologists the ability to study increasingly complex systems. A new methodology is needed to develop and test biological models based on experimental observations and predict the effect of perturbations of the network (e.g. genetic engineering, pharmaceuticals, gene therapy). Diverse modeling approaches have been proposed, in two general categories: modeling a biological pathway as (a) a logical circuit or (b) a chemical reaction network. Boolean logic models can not represent necessary biological details. Chemical kinetics simulations require large numbers of parameters that are very difficult to accurately measure. Based on the way biologists have traditionally thought about systems, we propose that fuzzy logic is a natural language for modeling biology. The Union Rule Configuration (URC) avoids combinatorial explosion in the fuzzy rule base, allowing complex system models. We demonstrate the fuzzy modeling method on the commonly studied lac operon of E. coli. Our goal is to develop a modeling and simulation approach that can be understood and applied by biologists without the need for experts in other fields or "black-box" software.

[1]  D. Endy,et al.  Computation, prediction, and experimental tests of fitness for bacteriophage T7 mutants with permuted genomes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

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

[3]  Jeffrey W. Roberts,et al.  遺伝子の分子生物学 = Molecular biology of the gene , 1970 .

[4]  Lotfi A. Zadeh,et al.  Fuzzy Sets , 1996, Inf. Control..

[5]  James E. Andrews,et al.  Combinatorial rule explosion eliminated by a fuzzy rule configuration , 1998, IEEE Trans. Fuzzy Syst..

[6]  S Fuhrman,et al.  Reveal, a general reverse engineering algorithm for inference of genetic network architectures. , 1998, Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing.

[7]  J. Fitch,et al.  Genomic engineering: moving beyond DNA sequence to function , 2000, Proceedings of the IEEE.

[8]  A. Arkin,et al.  Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells. , 1998, Genetics.

[9]  J. Mendel Fuzzy logic systems for engineering: a tutorial , 1995, Proc. IEEE.

[10]  G Sassi,et al.  Macro Approach and Fuzzy Modeling of Entrapped Biocatalyst , 2000, Biotechnology progress.

[11]  Lotfi A. Zadeh,et al.  Outline of a New Approach to the Analysis of Complex Systems and Decision Processes , 1973, IEEE Trans. Syst. Man Cybern..

[12]  L Yang,et al.  Incorporating qualitative knowledge in enzyme kinetic models using fuzzy logic. , 1999, Biotechnology and bioengineering.

[13]  H. Zimmermann,et al.  Fuzzy Set Theory and Its Applications , 1993 .

[14]  P. Woolf,et al.  A fuzzy logic approach to analyzing gene expression data. , 2000, Physiological genomics.