کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5760129 1623791 2017 21 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Global sensitivity analysis of a model related to memory formation in synapses: Model reduction based on epistemic parameter uncertainties and related issues
ترجمه فارسی عنوان
تجزیه و تحلیل حساسیت جهانی یک مدل مربوط به تشکیل حافظه در سیناپس: کاهش مدل بر اساس عدم قطعیت پارامتر معرفت شناختی و مسائل مرتبط
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی
We investigate the epistemic uncertainties of parameters of a mathematical model that describes the dynamics of CaMKII-NMDAR complex related to memory formation in synapses using global sensitivity analysis (GSA). The model, which was published in this journal, is nonlinear and complex with Ca2+ patterns with different level of frequencies as inputs. We explore the effects of parameter on the key outputs of the model to discover the most sensitive ones using GSA and partial ranking correlation coefficient (PRCC) and to understand why they are sensitive and others are not based on the biology of the problem. We also extend the model to add presynaptic neurotransmitter vesicles release to have action potentials as inputs of different frequencies. We perform GSA on this extended model to show that the parameter sensitivities are different for the extended model as shown by PRCC landscapes. Based on the results of GSA and PRCC, we reduce the original model to a less complex model taking the most important biological processes into account. We validate the reduced model against the outputs of the original model. We show that the parameter sensitivities are dependent on the inputs and GSA would make us understand the sensitivities and the importance of the parameters. A thorough phenomenological understanding of the relationships involved is essential to interpret the results of GSA and hence for the possible model reduction.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Theoretical Biology - Volume 419, 21 April 2017, Pages 116-136
نویسندگان
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