Herold Sebastian, King Rudibert
Chair of Measurement and Control, Technische Universität Berlin, Secr. ER 2-1, Hardenbergstraße 36a, 10623, Berlin, Germany,
Bioprocess Biosyst Eng. 2014 Jul;37(7):1289-304. doi: 10.1007/s00449-013-1100-6. Epub 2013 Dec 10.
In this paper, we present a set of methods to automatically propose structured process models from an automated analysis of (fed-)batch experiments. Therefore, the measurements are numerically compensated for the influence of feeding and sampling, and the qualitative behavior of the measurements is revealed. As measurements from fermentations are inherently noisy, we introduce a method that divides the compensated curves into several episodes in a probabilistic framework to better handle these shortcomings. The probability of biological phenomena that reveal crucial information about the underlying reaction network is calculated. Since the phenomena detection is measurement-driven, its reliability depends on the measurement situation, e.g., the number of samples taken and experiments considered, measurement noise, etc. We show a possible approach to test the uncertainty of the phenomena detection against these influences. Finally, model structures are proposed automatically based on the detected biological phenomena. An experimental validation of the approach is shown, using real fermentation data from fed-batch cultivations of Streptomyces tendae.
