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Motif modeling for cell signaling networks

Network motifs are recurring regulation patterns that appear in different biological networks such as cell signaling, gene regulatory, and metabolic networks. In this paper, we introduce a modeling scheme for cell signaling network motifs including gene expression, receptor activation, and translocation of cellular molecules. We incorporated these motifs into the executable model of T cell receptor (TCR) signaling pathway. The differentiation outcome of naïve T cells into regulatory and helper cells changes after adding network motifs into the executable model. Our simulation approach utilizes a randomized update scheme of a discrete logical model. The results show that the delays resulting from these motifs can change the effect of feedback and feed-forward loops on the amplitude and time of elements' transient behavior, as well as elements' steady-states. Overall, the proposed in silico modeling technique allows for more accurate recapitulation of observed in vitro experimental results.