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

Gross, Fridolin and Green, Sara (2017) The Sum of the Parts: Large-Scale Modeling in Systems Biology. Philosophy, Theory, and Practice in Biology, 9 (10). ISSN 2475-3025

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Abstract

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 would offer a superior approach. To address these questions, we distinguish between two types of reductionism which we call “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 rely on a number of idealizations and simplifying assumptions as well, we argue that they provide insight into the limitations of reductionist approaches. Whole-cell models can be used to discover properties arising at the interfaces of dynamically coupled processes within a biological system, thereby making more apparent what is lost through decomposition. Similarly, multi-scale modeling highlights the relevance 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.

Part of a special issue, Ontologies of Living Beings, guest-edited by A. M. Ferner and Thomas Pradeu


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Item Type: Published Article or Volume
Creators:
CreatorsEmailORCID
Gross, Fridolinfridolin.gross@uni-kassel.de
Green, Sarasara.green@ind.ku.dk
Keywords: heuristics, modeling, Multi-scale Cardiac, reductionism, simulations, Systems Biology, Whole-cell Modeling
Depositing User: Nora Boyd
Date Deposited: 06 Apr 2018 16:15
Last Modified: 06 Apr 2018 16:15
Item ID: 14541
Journal or Publication Title: Philosophy, Theory, and Practice in Biology
DOI or Unique Handle: 10.3998/ptb.6959004.0009.010
Date: 2017
Volume: 9
Number: 10
ISSN: 2475-3025
URI: https://philsci-archive.pitt.edu/id/eprint/14541

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