ArticlePLoS computational biology2009
ON/OFF and beyond--a boolean model of apoptosis.
Article in PLoS computational biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed.
- Unveiling toxicological adverse outcomes: toward construction and simulation of large-scale networks.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- p53 Orchestrates the Immunogenic-Tolerogenic Pyroptosis Switch in Non-Small Cell Lung Cancer: A Systems Biology Approach.Computational and structural biotechnology journal · 2026Article
- BioLogical: a universal analysis framework for biosystem logical dynamics.Computational and structural biotechnology journal · 2026Article
- Review
- A new model for the inference of biological entities states: Ternary Entity State Inference System.Heliyon · 2024Article
- A dynamic Boolean network reveals that the BMI1 and MALAT1 axis is associated with drug resistance by limiting miR-145-5p in non-small cell lung cancer.Non-coding RNA research · 2024Article
- Modulating the dynamics of NFκB and PI3K enhances the ensemble-level TNFR1 signaling mediated apoptotic response.NPJ systems biology and applications · 2023Article
- Article
- Automatic mechanistic inference from large families of Boolean models generated by Monte Carlo tree search.Frontiers in cell and developmental biology · 2023Article
- Mathematical Models of Death Signaling Networks.Entropy (Basel, Switzerland) · 2022Review
- Modulation of signaling cross-talk between pJNK and pAKT generates optimal apoptotic response.PLoS computational biology · 2022Article
- Predictive Modelling in Clinical Bioinformatics: Key Concepts for Startups.Biotech (Basel (Switzerland)) · 2022Article
- Mathematical modeling of the molecular switch of TNFR1-mediated signaling pathways applying Petri net formalism and in silico knockout analysis.PLoS computational biology · 2022Article
- A probabilistic Boolean model on hair follicle cell fate regulation by TGF-β.Biophysical journal · 2022Article
- LogicNet: probabilistic continuous logics in reconstructing gene regulatory networks.BMC bioinformatics · 2020Article
- Patient-specific logic models of signaling pathways from screenings on cancer biopsies to prioritize personalized combination therapies.Molecular systems biology · 2020Article
- A Probabilistic Approach to Explore Signal Execution Mechanisms With Limited Experimental Data.Frontiers in genetics · 2020Article
- Concepts in Boolean network modeling: What do they all mean?Computational and structural biotechnology journal · 2020Review
- A feedback loop of conditionally stable circuits drives the cell cycle from checkpoint to checkpoint.Scientific reports · 2019Article
- Controlling large Boolean networks with single-step perturbations.Bioinformatics (Oxford, England) · 2019Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis is regulated by several signaling pathways which are extensively linked by crosstalks. Boolean or logical modeling has become a promising approach to capture the qualitative behavior of such complex networks. Here we built a large-scale literature-based Boolean model of the central intrinsic and extrinsic apoptosis pathways as well as pathways connected with them. The model responds to several external stimuli such as Fas ligand, TNF-alpha, UV-B irradiation, interleukin-1beta and insulin. Timescales and multi-value node logic were used and turned out to be indispensable to reproduce the behavior of the apoptotic network. The coherence of the model was experimentally validated. Thereby an UV-B dose-effect is shown for the first time in mouse hepatocytes. Analysis of the model revealed a tight regulation emerging from high connectivity and spanning crosstalks and a particular importance of feedback loops. An unexpected feedback from Smac release to RIP could further increase complex II formation. The introduced Boolean model provides a comprehensive and coherent description of the apoptosis network behavior. It gives new insights into the complex interplay of pro- and antiapoptotic factors and can be easily expanded to other signaling pathways.
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