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Minimal frustration underlies the usefulness of incomplete and inexact regulatory network models in biology

View ORCID ProfileShubham Tripathi, David A. Kessler, Herbert Levine
doi: https://doi.org/10.1101/2022.06.07.495167
Shubham Tripathi
1PhD Program in Systems, Synthetic, and Physical Biology, Rice University, Houston, TX, USA
2Center for Theoretical Biological Physics & Department of Physics, Northeastern University, Boston, MA, USA
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  • For correspondence: shubtri@rice.edu
David A. Kessler
3Department of Physics, Bar-Ilan University, Ramat-Gan 52900, Israel
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Herbert Levine
2Center for Theoretical Biological Physics & Department of Physics, Northeastern University, Boston, MA, USA
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Abstract

Regulatory networks as large and complex as those implicated in cell-fate choice are expected to exhibit intricate, very high-dimensional dynamics. Cell-fate choice, however, is a macroscopically simple process. Additionally, regulatory network models are almost always incomplete and / or inexact, and do not incorporate all the regulators and interactions that may be involved in cellfate regulation. In spite of these issues, regulatory network models have proven to be incredibly effective tools for understanding cell-fate choice across contexts and for making useful predictions. Here, we show that minimal frustration—a feature of biological networks across contexts but not of random networks—can compel simple, low-dimensional steady-state behavior even in large and complex networks. Moreover, the steady-state behavior of minimally frustrated networks can be recapitulated by simpler networks such as those lacking many of the nodes and edges, and those that treat multiple regulators as one. The present study provides a theoretical explanation for the success of network models in biology and for the challenges in network inference.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† kessler{at}dave.ph.biu.ac.il

  • ↵‡ h.levine{at}northeastern.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 09, 2022.
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Minimal frustration underlies the usefulness of incomplete and inexact regulatory network models in biology
Shubham Tripathi, David A. Kessler, Herbert Levine
bioRxiv 2022.06.07.495167; doi: https://doi.org/10.1101/2022.06.07.495167
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Minimal frustration underlies the usefulness of incomplete and inexact regulatory network models in biology
Shubham Tripathi, David A. Kessler, Herbert Levine
bioRxiv 2022.06.07.495167; doi: https://doi.org/10.1101/2022.06.07.495167

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