Systematic analysis of noise reduction properties of coupled and isolated feed-forward loops.

Suchana Chakravarty,Attila Csikász-Nagy,Christopher Rao

doi:10.1371/journal.pcbi.1009622

Suchana Chakravarty, Attila Csikász-Nagy + Show 1 more

Open Access

https://doi.org/10.1371/journal.pcbi.1009622

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Abstract

Cells can maintain their homeostasis in a noisy environment since their signaling pathways can filter out noise somehow. Several network motifs have been proposed for biological noise filtering and, among these, feed-forward loops have received special attention. Specific feed-forward loops show noise reducing capabilities, but we notice that this feature comes together with a reduced signal transducing performance. In posttranslational signaling pathways feed-forward loops do not function in isolation, rather they are coupled with other motifs to serve a more complex function. Feed-forward loops are often coupled to other feed-forward loops, which could affect their noise-reducing capabilities. Here we systematically study all feed-forward loop motifs and all their pairwise coupled systems with activation-inactivation kinetics to identify which networks are capable of good noise reduction, while keeping their signal transducing performance. Our analysis shows that coupled feed-forward loops can provide better noise reduction and, at the same time, can increase the signal transduction of the system. The coupling of two coherent 1 or one coherent 1 and one incoherent 4 feed-forward loops can give the best performance in both of these measures.

Highlights

Random fluctuations in molecular levels causes noise in various biological processes [1,2,3]
Three component networks of feedforward loops (FFLs) have been proposed to serve as ideal noise reducers, while linear pathways were shown to be good signal transducers. These signaling units do not work in isolation, so there is a possibility that a combination of various feed-forward loops can provide good noise reduction, while maintaining good signal transduction
Coupled feed-forward loops can be categorized as multi-input coupled feed-forward loops (Fig 1C) and multi-intermediate coupled feed-forward loops (Fig 1D)

Summary

Introduction

Random fluctuations in molecular levels causes noise in various biological processes [1,2,3]. Extrinsic noises can be caused by the noisy environment around cells [4], whereas low-copy number molecules generate random fluctuations, which we term intrinsic noise [5,6,7]. This intrinsic noise is directly proportional to the square root of the number of molecules presents in system [8]. The resultant fluctuations in molecule numbers might result in increased noise in processes controlled by low-abundance molecules. Gene expression is a typical example, where a few copies of transcription factors influence the transcription [9] of several genes

Results

Discussion

Conclusion