| Task-oriented modular decomposition of biological networks: trigger mechanism in blood coagulation. | |
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MedLine Citation:
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PMID: 20441738 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Mikhail A Panteleev; Anna N Balandina; Elena N Lipets; Mikhail V Ovanesov; Fazoil I Ataullakhanov |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biophysical journal Volume: 98 ISSN: 1542-0086 ISO Abbreviation: Biophys. J. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-05 Completed Date: 2010-07-29 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0370626 Medline TA: Biophys J Country: United States |
Other Details:
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Languages: eng Pagination: 1751-61 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia. mapanteleev@yandex.ru |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Coagulation* Cysteine Endopeptidases / metabolism Factor V / metabolism Factor VIII / metabolism Factor X / metabolism Feedback, Physiological Fibrin / biosynthesis Humans Models, Biological* Neoplasm Proteins / metabolism Prothrombin / metabolism Rabbits Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Neoplasm Proteins; 9001-24-5/Factor V; 9001-26-7/Prothrombin; 9001-27-8/Factor VIII; 9001-29-0/Factor X; 9001-31-4/Fibrin; EC 3.4.22.-/Cysteine Endopeptidases; EC 3.4.22.26/cancer procoagulant |
| Comments/Corrections | |
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