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Register a new userEffects of feedback and feedforward loops on dynamics of transcriptional regulatory model networks
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We demonstrate the advantages of feedforward loops using a Boolean network, which is one of the discrete dynamical models for transcriptional regulatory networks. After comparing the dynamical behaviors of network embedded feedback and feedforward loops, we found that feedforward loops can provide higher temporal order (coherence) with lower entropy (randomness) in a temporal program of gene expression. In addition, complexity of the state space that increases with longer length of attractors and greater number of attractors is also reduced for networks with more feedforward loops. Feedback loops show opposite effects on dynamics of the networks. These results suggest that feedforward loops are one of the favorable local structures in biomolecular and neuronal networks.
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We demonstrate the effects of embedding subgraphs using a Boolean network, which is one of the discrete dynamical models for transcriptional regulatory networks. After comparing the dynamical properties of network embedded seven different subgraphs including feedback and feedforward subgraphs, we found that complexity of the state space that increases with longer length of attractors and greater number of attractors is reduced for networks with more feedforward subgraphs. In addition, feedforward subgraphs can also provide higher mutual information with lower entropy in a temporal program of gene expression. Networks with other six subgraphs show opposite effects on dynamics of the networks, is roughly consistent with Thomass conjecture. These results suggest that feedforward subgraphs are one of the favorable local structures in biological complex networks.
Identifying the mechanism of intercellular feedback regulation is critical for the basic understanding of tissue growth control in organisms. In this paper, we analyze a tissue growth model consisting of a single lineage of two cell types regulated by negative feedback signalling molecules that undergo spatial diffusion. By deriving the fixed points for the uniform steady states and carrying out linear stability analysis, phase diagrams are obtained analytically for arbitrary parameters of the model. Two different generic growth modes are found: blow-up growth and final-state controlled growth which are governed by the non-trivial fixed point and the trivial fixed point respectively, and can be sensitively switched by varying the negative feedback regulation on the proliferation of the stem cells. Analytic expressions for the characteristic time scales for these two growth modes are also derived. Remarkably, the trivial and non-trivial uniform steady states can coexist and a sharp transition occurs in the bistable regime as the relevant parameters are varied. Furthermore, the bi-stable growth properties allows for the external control to switch between these two growth modes. In addition, the condition for an early accelerated growth followed by a retarded growth can be derived. These analytical results are further verified by numerical simulations and provide insights on the growth behavior of the tissue. Our results are also discussed in the light of possible realistic biological experiments and tissue growth control strategy. Furthermore, by external feedback control of the concentration of regulatory molecules, it is possible to achieve a desired growth mode, as demonstrated with an analysis of boosted growth, catch-up growth and the design for the target of a linear growth dynamic.
Auto-regulatory feedback loops are one of the most common network motifs. A wide variety of stochastic models have been constructed to understand how the fluctuations in protein numbers in these loops are influenced by the kinetic parameters of the main biochemical steps. These models differ according to (i) which sub-cellular processes are explicitly modelled; (ii) the modelling methodology employed (discrete, continuous or hybrid); (iii) whether they can be analytically solved for the steady-state distribution of protein numbers. We discuss the assumptions and properties of the main models in the literature, summarize our current understanding of the relationship between them and highlight some of the insights gained through modelling.
Most methods for modelling dynamics posit just two time scales: a fast and a slow scale. But many applications, including many in continuum mechanics, possess a wide variety of space-time scales; often they possess a continuum of space-time scales. I discuss an approach to modelling the discretised dynamics of advection and diffusion with rigorous support for changing the resolved spatial grid scale by just a factor of two. The mapping of dynamics from a finer grid to a coarser grid is then iterated to generate a hierarchy of models across a wide range of space-time scales, all with rigorous support across the whole hierarchy. This approach empowers us with great flexibility in modelling complex dynamics over multiple scales.
We introduce a new structure for memory neural networks, called feedforward sequential memory networks (FSMN), which can learn long-term dependency without using recurrent feedback. The proposed FSMN is a standard feedforward neural networks equipped with learnable sequential memory blocks in the hidden layers. In this work, we have applied FSMN to several language modeling (LM) tasks. Experimental results have shown that the memory blocks in FSMN can learn effective representations of long history. Experiments have shown that FSMN based language models can significantly outperform not only feedforward neural network (FNN) based LMs but also the popular recurrent neural network (RNN) LMs.
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