Identifiability of nonlinear systems with application to HIV/AIDS models

In this note, we investigate different concepts of nonlinear identifiability in the generic sense. We work in the linear algebraic framework. Necessary and sufficient conditions are found for geometrical identifiability, algebraic identifiability and identifiability with known initial conditions. Relationships between different concepts are characterized. Constructive procedures are worked out for both generic geometrical and algebraic identifiability of nonlinear systems. As an application of the theory developed, we study the identifiability properties of a four dimensional model of HIV/AIDS. The questions answered in this study include the minimal number of measurement of the variables for a complete determination of all parameters and the best period of time to make such measurements. This information will be useful in formulating guidelines for clinical practice.

[1]  S. Glad Solvability of differential algebraic equations and inequalities: An algorithm , 1997, 1997 European Control Conference (ECC).

[2]  J. Milnor Topology from the differentiable viewpoint , 1965 .

[3]  R. Siliciano,et al.  Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection , 1997, Nature.

[4]  A. Isidori Control of Nonlinear Systems Via Dynamic State-Feedback , 1986 .

[5]  M. Fliess,et al.  Nonlinear observability, identifiability, and persistent trajectories , 1991, [1991] Proceedings of the 30th IEEE Conference on Decision and Control.

[6]  X. Xia ESTIMATION OF HIV/AIDS PARAMETERS , 2002 .

[7]  C. Moog,et al.  Nonlinear Control Systems: An Algebraic Setting , 1999 .

[8]  Xiaohua Xia,et al.  Estimation of HIV/AIDS parameters , 2003, Autom..

[9]  M. Nowak,et al.  Virus dynamics: Mathematical principles of immunology and virology , 2001 .

[10]  D. Kirschner,et al.  Optimal control of the chemotherapy of HIV , 1997, Journal of mathematical biology.

[11]  Alan S. Perelson,et al.  Mathematical Analysis of HIV-1 Dynamics in Vivo , 1999, SIAM Rev..

[12]  R. Siliciano,et al.  Viral Dynamics in HIV-1 Infection , 1998, Cell.

[13]  Martin A. Nowak,et al.  Viral dynamics in human immunodeficiency virus type 1 infection , 1995, Nature.

[14]  M. Fliess A note on the invertibility of nonlinear input-output differential systems , 1986 .

[15]  T. Tarn,et al.  New results for identifiability of nonlinear systems , 1987 .

[16]  A. Perelson,et al.  A Model for the Immune System Response to HIV: AZT Treatment Studies , 1993 .

[17]  Ghislaine Joly-Blanchard,et al.  Some effective approaches to check the identifiability of uncontrolled nonlinear systems , 2001 .

[18]  A. Krener,et al.  Nonlinear observers with linearizable error dynamics , 1985 .

[19]  C. Janeway Immunobiology: The Immune System in Health and Disease , 1996 .

[20]  A. Perelson,et al.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection , 1995, Nature.

[21]  Lennart Ljung,et al.  On global identifiability for arbitrary model parametrizations , 1994, Autom..

[22]  A. Perelson,et al.  Dynamics of HIV infection of CD4+ T cells. , 1993, Mathematical biosciences.