Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study.
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Date
2015-10
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Abstract
Various T-cell co-receptor molecules and calcium channel CRAC play a pivotal role in the maintenance of cell’s
functional responses by regulating the production of effector molecules (mostly cytokines) that aids in immune
clearance and also maintaining the cell in a functionally active state. Any defect in these co-receptor signalling
pathways may lead to an altered expression pattern of the effector molecules. To study the propagation of such defects
with time and their effect on the intracellular protein expression patterns, a comprehensive and largest pathway map of
T-cell activation network is reconstructed manually. The entire pathway reactions are then translated using logical
equations and simulated using the published time series microarray expression data as inputs. After validating the
model, the effect of in silico knock down of co-receptor molecules on the expression patterns of their downstream
proteins is studied and simultaneously the changes in the phenotypic behaviours of the T-cell population are predicted,
which shows significant variations among the proteins expression and the signalling routes through which the
response is propagated in the cytoplasm. This integrative computational approach serves as a valuable technique to
study the changes in protein expression patterns and helps to predict variations in the cellular behaviour.
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Keywords
Boolean model, co-receptors and CRAC channel, synchronous and asynchronous simulation, T-cell signalling pathway, temporal gene expression patterns
Citation
Ganguli Piyali, Chowdhury Saikat, Bhowmick Rupa, Sarkar Ram Rup. Temporal protein expression pattern in intracellular signalling cascade during T-cell activation: A computational study. Journal of Biosciences. 2015 Oct; 40(4): 769-789.