Department of Chemistry, University of Calcutta, 92 A P C Road, Kolkata, 700009, India.
Theory Biosci. 2021 Jun;140(2):139-155. doi: 10.1007/s12064-021-00338-6. Epub 2021 Mar 9.
Cells impose optimal noise control mechanism in diverse situations to cope with distinct environmental cues. Sometimes, it is desirable for the cell to utilize fluctuations for noise-driven processes. In other cases, noise can be harmful to the cell to show optimal fitness. It is, therefore, important to unravel the noise propagation mechanism inside the cell. Such noise controlling mechanism is accomplished by using gene transcription regulatory networks. One such gene regulatory network is feed-forward loop, having three regulatory nodes S, X and Y. Here, we consider the most abundant type 1 of coherent and incoherent feed-forward loops with both OR and AND logic functions, forming four different architectures. In OR logic function, the functions representing S and X act additively for the regulation of Y, while in AND logic function, the same functions (S and X) act multiplicatively for the regulation of Y. Measurement of susceptibility of the signal at output Y is done using elasticity of each regulation in FFLs. Using susceptibility, we demonstrate the nature of pathway integration by which one-step and two-step pathways get overlapped. The integration type is competitive for motifs having OR gate, while it is noncompetitive for the same with AND gate. The pathway integration property explains the output noise behavior of the motifs properly but cannot infer about the mechanism by which the upstream noise propagates to output. To account this, the total output noise is decomposed, which results in integrated noise as an additional noise source along with pathway-specific noise components. The integrated noise is found to appear as a consequence of integration between the pathways and has different functional characteristics explaining noise amplification and noise attenuation property of coherent and incoherent feed-forward loops, respectively. The noise decomposition also quantifies the contribution of different noise sources toward total noise. Finally, the noise propagation is being tuned as a function of input signal noise and its time scale of fluctuations, which shows considerable intrinsic noise strength and relatively slow relaxation time scale causes a higher degree of noise propagation in FFLs.
细胞在不同情况下施加最佳的噪声控制机制，以应对不同的环境线索。有时，细胞利用波动来进行噪声驱动的过程是可取的。在其他情况下，噪声可能对细胞有害，以表现出最佳的适应性。因此，揭示细胞内噪声传播机制非常重要。这种噪声控制机制是通过使用基因转录调控网络来实现的。基因调控网络之一是前馈回路，具有三个调节节点 S、X 和 Y。在这里，我们考虑了最丰富的类型 1 相干和非相干前馈回路，它们具有 OR 和 AND 逻辑功能，形成了四种不同的结构。在 OR 逻辑功能中，代表 S 和 X 的功能对 Y 的调节是相加的，而在 AND 逻辑功能中，相同的功能（S 和 X）对 Y 的调节是相乘的。使用弹性测量输出 Y 处信号的敏感性，弹性是在 FFL 中每个调节的特征。使用敏感性，我们展示了信号通路整合的性质，其中一步和两步通路重叠。对于具有 OR 门的基序，整合类型是竞争性的，而对于具有 AND 门的相同基序，整合类型是非竞争性的。通路整合特性可以很好地解释基序的输出噪声行为，但不能推断上游噪声传播到输出的机制。为了解决这个问题，对总输出噪声进行了分解，结果表明，集成噪声是一个附加的噪声源，与通路特定的噪声分量一起出现。发现集成噪声是由于通路之间的集成而出现的，它具有不同的功能特性，分别解释了相干和非相干前馈回路的噪声放大和噪声衰减特性。噪声分解还量化了不同噪声源对总噪声的贡献。最后，作为输入信号噪声及其波动时间尺度的函数，对噪声传播进行了调整，这表明 FFL 中的固有噪声强度相当大，相对较慢的弛豫时间尺度导致噪声传播程度更高。
