کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2076488 1079448 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Identification of potential targets in biological signalling systems through network perturbation analysis
موضوعات مرتبط
مهندسی و علوم پایه ریاضیات مدل‌سازی و شبیه سازی
پیش نمایش صفحه اول مقاله
Identification of potential targets in biological signalling systems through network perturbation analysis
چکیده انگلیسی

The network-based representation and analysis of biological systems contributes to a greater understanding of their structures and functions at different levels of complexity. These techniques can also be used to identify potential novel therapeutic targets based on the characterisation of vulnerable or highly influential network components. There is a need to investigate methods for estimating the impact of molecular perturbations. The prediction of high-impact or critical targets can aid in the identification of novel strategies for controlling the level of activation of specific, therapeutically relevant genes or proteins. Here, we report a new computational strategy for the analysis of the vulnerability of cellular signalling networks based on the quantitative assessment of the impact of large-scale, dynamic perturbations. To show the usefulness of this methodology, two complex signalling networks were analysed: the caspase-3 and the adenosine-regulated calcium signalling systems. This allowed us to estimate and rank the perturbation impact of the components defining these networks. Testable hypotheses about how these targets could modify the dynamic operation of the systems are provided. In the case of the caspase-3 system, the predictions and rankings were in line with results obtained from previous experimental validations of computational predictions generated by a relatively more computationally complex technique. In the case of the adenosine-regulated calcium system, we offer new testable predictions on the potential effect of different targets on the control of calcium flux. Unlike previous methods, the proposed approach provides perturbation-specific scores for each network component. The proposed perturbation assessment methodology may be applied to other systems to gain a deeper understanding of their dynamic operation and to assist the discovery of new therapeutic targets and strategies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biosystems - Volume 100, Issue 1, April 2010, Pages 55–64
نویسندگان
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