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Application of Global Sensitivity Analysis to Determine Goals for Design of Experiments: An Example Study on Antibody‐Producing Cell Cultures
Author(s) -
Kontoravdi Cleo,
Asprey Steven P.,
Pistikopoulos Efstratios N.,
Mantalaris Athanasios
Publication year - 2008
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp050028k
Subject(s) - sobol sequence , sensitivity (control systems) , biological system , set (abstract data type) , computer science , contrast (vision) , experimental data , biochemical engineering , mathematical optimization , mathematics , statistics , biology , artificial intelligence , engineering , electronic engineering , programming language
Global sensitivity analysis (GSA) can be used to quantify the importance of model parameters and their interactions with respect to model output. In this study, the Sobol′ method for GSA is applied to a dynamic model of monoclonal antibody‐producing mammalian cell cultures in order to identify the parameters that need to be accurately determined experimentally. Our results show that most parameters have low sensitivity indices and exhibit strong interactions with one another. These parameters can be set at their nominal values and unnecessary experimentation can therefore be avoided. In contrast, certain parameters are identified as sensitive, necessitating their estimation given sufficiently rich experimental data. Moreover, parameter sensitivity varies during culture time in a biologically meaningful manner. In conclusion, GSA can serve as an excellent precursor to optimal experiment design.