Strategies for computer modeling.

Modeling is a ubiquitous and often misunderstood enterprise in which data from diverse disciplines are analyzed by techniques from other diverse disciplines in an attempt to confirm or falsify a set of hypotheses about the real world. Guidelines are offered for designing models to match the goals of modeling biological systems. Techniques for the construction and interpretation of models are discussed. The requirements for credibility of models are detailed, and tests are suggested for their validation.

[1]  M. Kohn,et al.  Sensitivity to values of the rate constants in a neurochemical metabolic model. , 1983, Journal of theoretical biology.

[2]  N. Shapiro,et al.  Stiff differential equations. , 1977, Annual review of biophysics and bioengineering.

[3]  L B Sheiner,et al.  Estimating population kinetics. , 1982, Critical reviews in biomedical engineering.

[4]  L B Sheiner,et al.  Pharmacokinetic and pharmacodynamic modeling in vivo. , 1981, Critical reviews in bioengineering.

[5]  M. Eslami,et al.  Introduction to System Sensitivity Theory , 1980, IEEE Transactions on Systems, Man, and Cybernetics.

[6]  F E Yates,et al.  Good manners in good modeling: mathematical models and computer simulations of physiological systems. , 1978, The American journal of physiology.

[7]  D Garfinkel,et al.  A convenient computer program for estimation of enzyme and metabolite concentrations in multienzyme systems. , 1981, Computers and biomedical research, an international journal.

[8]  Reinhart Heinrich,et al.  Mathematical analysis of multienzyme systems. II. Steady state and transient control. , 1975, Bio Systems.

[9]  D Garfinkel.  Computer modeling, complex biological systems, and their simplifications. , 1980, The American journal of physiology.

[10]  L. Anderson.  Decoupling of two-time-scale linear systems , 1978 .

[11]  M. Milanese,et al.  Advanced modeling and identification techniques for metabolic processes. , 1984, Critical reviews in biomedical engineering.

[12]  M C Kohn,et al.  A graph-theoretical analysis of metabolic regulation. , 1983, Journal of theoretical biology.

[13]  H. Kacser,et al.  MOlecular democracy: who shares the controls? , 1979, Biochemical Society transactions.

[14]  D Garfinkel,et al.  Systems analysis in enzyme kinetics. , 1977, CRC critical reviews in bioengineering.

[15]  M. Kohn,et al.  Metabolic network sensitivity analysis. , 1982, Journal of theoretical biology.

[16]  Gruia-Catalin Roman,et al.  A Method for Solving Certain Stiff Differential Equations. , 1978 .

[17]  Lawrence F. Shampine,et al.  A User’s View of Solving Stiff Ordinary Differential Equations , 1979 .

[18]  M. Kohn,et al.  Computer simulation of the fructose bisphosphatase/phosphofructokinase couple in rat liver. , 1979, European journal of biochemistry.

[19]  D Garfinkel,et al.  Computer simulation of metabolism in pyruvate-perfused rat heart. I. Model construction. , 1979, The American journal of physiology.

[20]  Computer simulation of metabolism in pyruvate-perfused rat heart. II. Krebs cycle. , 1979, The American journal of physiology.

[21]  Gruia-Catalin Roman,et al.  Construction of more reliable complex metabolic models without repeated solution of their constituent differential equations , 1978 .

[22]  A. Fabiato,et al.  Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum , 1983 .

[23]  Beyond the binary case in random nets , 1984 .

[24]  David Mautner Himmelblau,et al.  Decomposition of large-scale problems , 1973 .

[25]  C. W. Gear,et al.  The automatic integration of ordinary differential equations , 1971, Commun. ACM.

[26]  B. Wright,et al.  An analysis of the kinetic positions held by five enzymes of carbohydrate metabolism in Dictyostelium discoideum. , 1975, The Journal of biological chemistry.

[27]  D C Mikulecky.  Network thermodynamics: a candidate for a common language for theoretical and experimental biology. , 1983, The American journal of physiology.

[28]  Stability of multienzyme systems with feedback regulation: a graph theoretical approach. , 1985, Journal of theoretical biology.

[29]  S. D. Bedrosian,et al.  Information Flow and Complexity in Large-Scale Metabolic Systems , 1985 .

[30]  Salvador González,et al.  Modularization guidelines in the development of large-scale system models for simulation , 1985, IEEE Transactions on Systems, Man, and Cybernetics.