The Sum of the Parts: Large-scale Modeling in Systems Biology

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Systems biologists often distance themselves from reductionist approaches and formulate their aim as understanding living systems “as a whole”. Yet, it is often unclear what kind of reductionism they have in mind, and in what sense their methodologies offer a more comprehensive approach. To address these questions, we distinguish between two types of reductionism, namely 'modular reductionism' and 'bottom-up reductionism'. Much knowledge in molecular biology has been gained by decomposing living systems into functional modules or through detailed studies of molecular processes. We ask whether systems biology provides novel ways to ​ ​recompose these findings in the context of the system as a whole via computational simulations. As an example of computational integration of modules, we analyze the first whole-cell model of the bacterium ​ ​M. genitalium. Secondly, we examine the attempt to recompose processes across different spatial scales via multi-scale cardiac models. Although these models also rely on a number of idealizations and simplifying assumptions, we argue that they provide insight into the limitations of reductionist approaches. Whole-cell models can be used to discover properties arising at the interface of dynamically coupled processes within a biological system, thereby making more apparent what is lost through decomposition. Similarly, multi-scale modeling highlights the importance of macroscale parameters and models and challenges the view that living systems can be understood “bottom-up”. Specifically, we point out that system-level properties constrain lower-scale processes. Thus, large-scale modeling reveals how living systems at the ​same time ​ are ​more and ​less than the sum of the parts.
Original languageEnglish
JournalPhilosophy and Theory in Biology
Issue number10
Pages (from-to)1-26
Publication statusPublished - 2017

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