ArticleBiophysical journal2010
Task-oriented modular decomposition of biological networks: trigger mechanism in blood coagulation.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Trial
- In silico analysis of patient specific coagulation and flow effects on fibrin clot formation.Scientific reports · 2026Article
- Heparin and Direct Oral Anticoagulants have Different Effects on the Phases of Activation and Spatial Spread of Blood Coagulation.Thrombosis and haemostasis · 2026Article
- Biophysical perspectives of the spatiotemporal dynamics of plasma coagulation under flow.Biophysical reviews · 2025Review
- A new look at TFPI inhibition of factor X activation.PLoS computational biology · 2024Article
- Chemical Adjustment of Fibrinolysis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- A Review of Quantitative Systems Pharmacology Models of the Coagulation Cascade: Opportunities for Improved Usability.Pharmaceutics · 2023Review
- Redistribution of TPA Fluxes in the Presence of PAI-1 Regulates Spatial Thrombolysis.Biophysical journal · 2020Article
- Reduced model to predict thrombin and fibrin during thrombosis on collagen/tissue factor under venous flow: Roles of γ'-fibrin and factor XIa.PLoS computational biology · 2019Article
- Rat liver folate metabolism can provide an independent functioning of associated metabolic pathways.Scientific reports · 2019Article
- Sensitivity and Robustness of Spatially Dependent Thrombin Generation and Fibrin Clot Propagation.Biophysical journal · 2018Article
- Article
- Methylation potential associated with diet, genotype, protein, and metabolite levels in the Delta Obesity Vitamin Study.Genes & nutrition · 2014Article
- Coagulation makes waves.Biophysical journal · 2012Article
- Thrombin activity propagates in space during blood coagulation as an excitation wave.Biophysical journal · 2012Article
- Positive feedback loops for factor V and factor VII activation supply sensitivity to local surface tissue factor density during blood coagulation.Biophysical journal · 2011Article
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Authors and funding
5 authors.
Funding
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Abstract
Analysis of complex time-dependent biological networks is an important challenge in the current postgenomic era. We propose a middle-out approach for decomposition and analysis of complex time-dependent biological networks based on: 1), creation of a detailed mechanism-driven mathematical model of the network; 2), network response decomposition into several physiologically relevant subtasks; and 3), subsequent decomposition of the model, with the help of task-oriented necessity and sensitivity analysis into several modules that each control a single specific subtask, which is followed by further simplification employing temporal hierarchy reduction. The technique is tested and illustrated by studying blood coagulation. Five subtasks (threshold, triggering, control by blood flow velocity, spatial propagation, and localization), together with responsible modules, can be identified for the coagulation network. We show that the task of coagulation triggering is completely regulated by a two-step pathway containing a single positive feedback of factor V activation by thrombin. These theoretical predictions are experimentally confirmed by studies of fibrin generation in normal, factor V-, and factor VIII-deficient plasmas. The function of the factor V-dependent feedback is to minimize temporal and parametrical intervals of fibrin clot instability. We speculate that this pathway serves to lessen possibility of fibrin clot disruption by flow and subsequent thromboembolism.
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