Uncovering bifurcation behaviors of biochemical reaction systems from network topology
Abstract The regulation of biological functions is achieved through the modulation of biochemical reaction network dynamics. The diversity of cell states and the transitions between them have been interpreted as bifurcations in these dynamics. However, due to the complexity of networks and limited k...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-10688-6 |
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| author | Yong-Jin Huang Takashi Okada Atsushi Mochizuki |
| author_facet | Yong-Jin Huang Takashi Okada Atsushi Mochizuki |
| author_sort | Yong-Jin Huang |
| collection | DOAJ |
| description | Abstract The regulation of biological functions is achieved through the modulation of biochemical reaction network dynamics. The diversity of cell states and the transitions between them have been interpreted as bifurcations in these dynamics. However, due to the complexity of networks and limited knowledge of reaction kinetics, bifurcation behaviors in biological systems remain largely underexplored. To address this, we developed a mathematical method, Structural Bifurcation Analysis (SBA), which decomposes the system into substructures and determines important aspects of bifurcation behaviors—such as substructures responsible for bifurcation conditions, bifurcation-inducing parameters, and bifurcating variables—solely from network topology. We establish a direct relationship between SBA and classical bifurcation analysis, enabling the study of systems even in the presence of conserved quantities. Additionally, we provide a step-by-step bifurcation analysis for general use. We applied our method to the macrophage M1/M2 polarization system. Our analysis reveals that the network structure strongly constrains possible patterns of polarization. We also clarify the dependency of the M1/M2 balance on gene expression levels and predict the emergence of intermediate polarization patterns under gene deletions, including SOCS3, which are experimentally testable. |
| format | Article |
| id | doaj-art-bbcf7f15cce34647acab3d979dcadfdc |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-bbcf7f15cce34647acab3d979dcadfdc2025-08-20T03:05:25ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-10688-6Uncovering bifurcation behaviors of biochemical reaction systems from network topologyYong-Jin Huang0Takashi Okada1Atsushi Mochizuki2Institute for Life and Medical Sciences, Kyoto UniversityInstitute for Life and Medical Sciences, Kyoto UniversityInstitute for Life and Medical Sciences, Kyoto UniversityAbstract The regulation of biological functions is achieved through the modulation of biochemical reaction network dynamics. The diversity of cell states and the transitions between them have been interpreted as bifurcations in these dynamics. However, due to the complexity of networks and limited knowledge of reaction kinetics, bifurcation behaviors in biological systems remain largely underexplored. To address this, we developed a mathematical method, Structural Bifurcation Analysis (SBA), which decomposes the system into substructures and determines important aspects of bifurcation behaviors—such as substructures responsible for bifurcation conditions, bifurcation-inducing parameters, and bifurcating variables—solely from network topology. We establish a direct relationship between SBA and classical bifurcation analysis, enabling the study of systems even in the presence of conserved quantities. Additionally, we provide a step-by-step bifurcation analysis for general use. We applied our method to the macrophage M1/M2 polarization system. Our analysis reveals that the network structure strongly constrains possible patterns of polarization. We also clarify the dependency of the M1/M2 balance on gene expression levels and predict the emergence of intermediate polarization patterns under gene deletions, including SOCS3, which are experimentally testable.https://doi.org/10.1038/s41598-025-10688-6 |
| spellingShingle | Yong-Jin Huang Takashi Okada Atsushi Mochizuki Uncovering bifurcation behaviors of biochemical reaction systems from network topology Scientific Reports |
| title | Uncovering bifurcation behaviors of biochemical reaction systems from network topology |
| title_full | Uncovering bifurcation behaviors of biochemical reaction systems from network topology |
| title_fullStr | Uncovering bifurcation behaviors of biochemical reaction systems from network topology |
| title_full_unstemmed | Uncovering bifurcation behaviors of biochemical reaction systems from network topology |
| title_short | Uncovering bifurcation behaviors of biochemical reaction systems from network topology |
| title_sort | uncovering bifurcation behaviors of biochemical reaction systems from network topology |
| url | https://doi.org/10.1038/s41598-025-10688-6 |
| work_keys_str_mv | AT yongjinhuang uncoveringbifurcationbehaviorsofbiochemicalreactionsystemsfromnetworktopology AT takashiokada uncoveringbifurcationbehaviorsofbiochemicalreactionsystemsfromnetworktopology AT atsushimochizuki uncoveringbifurcationbehaviorsofbiochemicalreactionsystemsfromnetworktopology |