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Complexity reduction preserving dynamical behavior of biochemical networks
Apri M.a,b,c, de Gee M.a,b, Molenaar J.a,b
a Wageningen University and Research Center, Netherlands
b Netherlands Consortium for Systems Biology, Netherlands
c Industrial and Financial Mathematics Group, Bandung Institute of Technology, Indonesia
[vc_row][vc_column][vc_row_inner][vc_column_inner][vc_separator css=”.vc_custom_1624529070653{padding-top: 30px !important;padding-bottom: 30px !important;}”][/vc_column_inner][/vc_row_inner][vc_row_inner layout=”boxed”][vc_column_inner width=”3/4″ css=”.vc_custom_1624695412187{border-right-width: 1px !important;border-right-color: #dddddd !important;border-right-style: solid !important;border-radius: 1px !important;}”][vc_empty_space][megatron_heading title=”Abstract” size=”size-sm” text_align=”text-left”][vc_column_text]The complexity of biochemical systems, stemming from both the large number of components and the intricate interactions between these components, may hinder us in understanding the behavior of these systems. Therefore, effective methods are required to capture their key components and interactions. Here, we present a novel and efficient reduction method to simplify mathematical models of biochemical systems. Our method is based on the exploration of the so-called admissible region, that is the set of parameters for which the mathematical model yields some required output. From the shape of the admissible region, parameters that are really required in generating the output of the system can be identified and hence retained in the model, whereas the rest is removed.To describe the idea, first the admissible region of a very small artificial network with only three nodes and three parameters is determined. Despite its simplicity, this network reveals all the basic ingredients of our reduction method. The method is then applied to an epidermal growth factor receptor (EGFR) network model. It turns out that only about 34% of the network components are required to yield the correct response to the epidermal growth factor (EGF) that was measured in the experiments, whereas the rest could be considered as redundant for this purpose. Furthermore, it is shown that parameter sensitivity on its own is not a reliable tool for model reduction, because highly sensitive parameters are not always retained, whereas slightly sensitive parameters are not always removable. © 2012 Elsevier Ltd.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Author keywords” size=”size-sm” text_align=”text-left”][vc_column_text][/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Indexed keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Admissible region,Complexity reduction,Dynamical behavior,Parameter estimation,Sloppy parameters[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Funding details” size=”size-sm” text_align=”text-left”][vc_column_text]This work was carried out within the research programme of the Netherlands Consortium for Systems Biology (NCSB), which is part of the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”DOI” size=”size-sm” text_align=”text-left”][vc_column_text]https://doi.org/10.1016/j.jtbi.2012.03.019[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_column_text]Widget Plumx[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row][vc_column][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][/vc_column][/vc_row]