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Task-oriented modular decomposition of biological networks: trigger mechanism in blood coagulationстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
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Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Panteleev Mikhail A., Balandina Anna N., Lipets Elena N., Ovanesov Mikhail V., Ataullakhanov Fazoil I.
- Журнал: Biophysical Journal
- Том: 98
- Номер: 9
- Год издания: 2010
- Издательство: Biophysical Society
- Местоположение издательства: United States
- Первая страница: 1751
- Последняя страница: 1761
- DOI: 10.1016/j.bpj.2010.01.027
- Аннотация: 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.
- Добавил в систему: Пантелеев Михаил Александрович