REGULATORY NETWORKS UNDER ELLIPSOIDAL UNCERTAINTY - OPTIMIZATION THEORY AND DYNAMICAL SYSTEMS

In this paper, we introduce and analyze time-discrete target-environment regulatory systems (TEsystems) under ellipsoidal uncertainty. The uncertain states of clusters of target and environmental items of the regulatory system are represented in terms of ellipsoids and the interactions between the various clusters are defined by affine-linear coupling rules. The parameters of the coupling rules and the time-dependent states of clusters define the regulatory network. Explicit representations of the uncertain multivariate states of the system are determined with ellipsoidal calculus. In addition, we introduce various regression models that allow us to determine the unknown system parameters from uncertain (ellipsoidal) measurement data by applying semidefinite programming and interior point methods. Finally, we turn to rarefications of the regulatory network. We present a corresponding mixed integer regression problem and achieve a further relaxation by means of continuous optimization. We analyze the structure of the optimization problems obtained, especially, in view of their solvability, we discuss the structural frontiers and research challenges, and we conclude with an outlook.

[1]  Werner Krabs,et al.  Dynamische Systeme: Steuerbarkeit und chaotisches Verhalten , 1998 .

[2]  Röbbe Wünschiers,et al.  Genetic Networks and Anticipation of Gene Expression Patterns , 2004 .

[3]  Erik Kropat,et al.  OPTIMIZATION APPLIED ON REGULATORY AND ECO-FINANCE NETWORKS - SURVEY AND NEW DEVELOPMENTS - , 2010 .

[4]  Hidde de Jong,et al.  Modeling and Simulation of Genetic Regulatory Systems: A Literature Review , 2002, J. Comput. Biol..

[5]  Röbbe Wünschiers,et al.  An algorithm to analyze stability of gene-expression patterns , 2006, Discret. Appl. Math..

[6]  U. Alon,et al.  Environmental variability and modularity of bacterial metabolic networks , 2007, BMC Evolutionary Biology.

[7]  Rodica Branzei,et al.  Cooperative interval games: a survey , 2010, Central Eur. J. Oper. Res..

[8]  Mesut Tastan,et al.  ANALYSIS AND PREDICTION OF GENE EXPRESSION PATTERNS BY DYNAMICAL SYSTEMS, AND BY A COMBINATORIAL ALGORITHM , 2005 .

[9]  Harris,et al.  Using genes and environments to define asthma and related phenotypes: applications to multivariate data , 1998, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[10]  Robert Tibshirani,et al.  Discriminant Adaptive Nearest Neighbor Classification , 1995, IEEE Trans. Pattern Anal. Mach. Intell..

[11]  Erik Kropat,et al.  Eco-Finance Networks under Uncertainty , 2008 .

[12]  Federico Thomas,et al.  An ellipsoidal calculus based on propagation and fusion , 2002, IEEE Trans. Syst. Man Cybern. Part B.

[13]  Zeev Volkovich,et al.  On a Minimal Spanning Tree Approach in the Cluster Validation Problem , 2009, Informatica.

[14]  Rodica Branzei,et al.  Convex Interval Games , 2009, Adv. Decis. Sci..

[15]  R. Hardt,et al.  Real homotopy theory of semi-algebraic sets , 2008, 0806.0476.

[16]  Gerhard-Wilhelm Weber,et al.  Generalized semi-infinite optimization and related topics , 1999 .

[17]  Isaac Elishakoff,et al.  Whys and hows in uncertainty modelling : probability, fuzziness and anti-optimization , 1999 .

[18]  G. Weber,et al.  MODELING AND PREDICTION OF GENE-EXPRESSION PATTERNS RECONSIDERED WITH RUNGEKUTTA DISCRETIZATION , 2004 .

[19]  Marie-Françoise Roy,et al.  Real algebraic geometry , 1992 .

[20]  Adil M. Bagirov,et al.  Piecewise Partially Separable Functions and a Derivative-free Algorithm for Large Scale Nonsmooth Optimization , 2006, J. Glob. Optim..

[21]  Satoru Miyano,et al.  Inferring Gene Regulatory Networks from Time-Ordered Gene Expression Data of Bacillus Subtilis Using Differential Equations , 2002, Pacific Symposium on Biocomputing.

[22]  Alexander Shapiro,et al.  Lectures on Stochastic Programming: Modeling and Theory , 2009 .

[23]  Clifford H. Thurber,et al.  Parameter estimation and inverse problems , 2005 .

[24]  G.,et al.  Stability Analysis of Gene Expression Patterns by Dynamical Systems and a Combinatorial Algorithm , 2005 .

[25]  Gerhard-Wilhelm Weber,et al.  New Optimization Methods in Data Mining , 2009 .

[26]  Yi-Fan Li,et al.  Modeling global emissions and residues of pesticides , 2005 .

[27]  Gerhard-Wilhelm Weber,et al.  Mathematical Modeling and Approximation of Gene Expression Patterns , 2004, OR.

[28]  Qingzhong Liu,et al.  Supervised learning-based tagSNP selection for genome-wide disease classifications , 2008, BMC Genomics.

[29]  Werner Krabs,et al.  A Game-Theoretic Treatment of a Time-Discrete Emission Reduction Model , 2004, IGTR.

[30]  Aharon Ben-Tal,et al.  Lectures on modern convex optimization , 1987 .

[31]  Jonei Cerqueira Barbosa,et al.  What is Mathematical Modelling , 2003 .

[32]  Thorsten Theobald,et al.  Positive Polynome und semidefinite Optimierung , 2008 .

[33]  Gerhard-Wilhelm Weber,et al.  On optimization, dynamics and uncertainty: A tutorial for gene-environment networks , 2009, Discret. Appl. Math..

[34]  Elhanan Borenstein,et al.  Topological Signatures of Species Interactions in Metabolic Networks , 2009, J. Comput. Biol..

[35]  J. Gebert,et al.  Inference of Gene Expression Patterns by Using a Hybrid System Formulation An Algorithmic Approach to Local State Transition Matrices , 2004 .

[36]  Boris Polyak,et al.  Multi-Input Multi-Output Ellipsoidal State Bounding , 2001 .

[37]  J. Risler,et al.  Real algebraic and semi-algebraic sets , 1990 .

[38]  Fatma Byilmaz A MATHEMATICAL MODELING AND APPROXIMATION OF GENE EXPRESSION PATTERNS BY LINEAR AND QUADRATIC REGULATORY RELATIONS AND ANALYSIS OF GENE NETWORKS , 2004 .

[39]  Yurii Nesterov,et al.  Interior-point polynomial algorithms in convex programming , 1994, Siam studies in applied mathematics.

[40]  Gerhard-Wilhelm Weber,et al.  Optimization and dynamics of gene-environment networks with intervals , 2007 .

[41]  Gerhard-Wilhelm Weber,et al.  CLUSTER ALGORITHMS: THEORY AND METHODS ¤ , 2002 .

[42]  Erik Kropat,et al.  A review on data mining and continuous optimization applications in computational biology and medicine. , 2009, Birth defects research. Part C, Embryo today : reviews.

[43]  Stephen P. Boyd,et al.  An ellipsoidal approximation to the Hadamard product of ellipsoids , 2002, 2002 IEEE International Conference on Acoustics, Speech, and Signal Processing.

[44]  Gerhard-Wilhelm Weber,et al.  Mathematical contributions to dynamics and optimization of gene-environment networks , 2008 .

[45]  G. Weber,et al.  Environmental and life sciences: gene-environment networks optimization, games and control a survey on recent achievements , 2008 .

[46]  A. Kurzhanski,et al.  Ellipsoidal Calculus for Estimation and Control , 1996 .

[47]  Erik Kropat,et al.  A survey on OR and mathematical methods applied on gene-environment networks , 2009, Central Eur. J. Oper. Res..

[48]  J. Gebert,et al.  Analyzing and optimizing genetic network structure via path-finding , 2004 .

[49]  Zeev Volkovich,et al.  CLUSTER STABILITY ESTIMATION BASED ON A MINIMAL SPANNING TREES APPROACH , 2009 .

[50]  G.-W. Weber,et al.  A New Mathematical Approach in Environmental and Life Sciences: Gene–Environment Networks and Their Dynamics , 2009 .

[51]  G. Weber,et al.  OPTIMIZATION OF A TIME-DISCRETE NONLINEAR DYNAMICAL SYSTEM FROM A PROBLEM OF ECOLOGY. AN ANALYTICAL AND NUMERICAL APPROACH , 2001 .

[52]  Pravin Varaiya,et al.  ELLIPSOIDAL TOOLBOX 1 Manual , 2007 .

[53]  Gerhard-Wilhelm Weber,et al.  On generalized semi-infinite optimization of genetic networks , 2007 .

[54]  P. Taylan,et al.  New approaches to regression by generalized additive models and continuous optimization for modern applications in finance, science and technology , 2007 .

[55]  P. Taylan,et al.  NEW APPROACHES TO REGRESSION IN FINANCIAL MATHEMATICS BY ADDITIVE MODELS , 2007 .

[56]  Stephen P. Boyd,et al.  Convex Optimization , 2004, Algorithms and Theory of Computation Handbook.

[57]  Trevor Hastie,et al.  The Elements of Statistical Learning , 2001 .

[58]  Stefan Wolfgang Pickl,et al.  Der t-value als Kontrollparameter: Modellierung und Analyse eines Joint-Implementation-Programmes mithilfe der dynamischen kooperativen Spieltheorie und der Diskreten Optimierung , 1999 .

[59]  Gerhard-Wilhelm Weber,et al.  Modeling gene regulatory networks with piecewise linear differential equations , 2007, Eur. J. Oper. Res..

[60]  Rodica Branzei,et al.  Airport interval games and their Shapley value , 2009 .

[61]  Joseph Priestley,et al.  Operational Research Meets Biology: An Algorithmic Approach to Analyze Genetic Networks and Biological Energy Production , .

[62]  Gerhard-Wilhelm Weber,et al.  A new approach to multivariate adaptive regression splines by using Tikhonov regularization and continuous optimization , 2010 .

[63]  Ting Chen,et al.  Modeling Gene Expression with Differential Equations , 1998, Pacific Symposium on Biocomputing.

[65]  Adil M. Bagirov,et al.  A new nonsmooth optimization algorithm for minimum sum-of-squares clustering problems , 2006, Eur. J. Oper. Res..

[66]  Silvia Miquel,et al.  Cooperation under interval uncertainty , 2008, Math. Methods Oper. Res..

[67]  S. Pickl An Iterative Solution to the Nonlinear Time‐Discrete TEM Model ‐ The Occurrence of Chaos and a Control Theoretic Algorithmic Approach , 2002 .