Network design principle for robust oscillatory behaviors with respect to biological noise

Oscillatory behaviors, which are ubiquitous in transcriptional regulatory networks, are often subject to inevitable biological noise. Thus a natural question is how transcriptional regulatory networks can robustly achieve accurate oscillation in the presence of biological noise. Here, we search all two- and three-node transcriptional regulatory network topologies for those robustly capable of accurate oscillation against the parameter variability (extrinsic noise) or stochasticity of chemical reactions (intrinsic noise). We find that, no matter what source of the noise is applied, the topologies containing the repressilator with positive auto-regulation show higher robustness of accurate oscillation than those containing the activator-inhibitor oscillator, and additional positive auto-regulation enhances the robustness against noise. Nevertheless, the attenuation of different sources of noise is governed by distinct mechanisms: the parameter variability is buffered by the long period, while the stochasticity of chemical reactions is filtered by the high amplitude. Furthermore, we analyze the noise of a synthetic human nuclear factor κB (NF-κB) signaling network by varying three different topologies, and verify that the addition of a repressilator to the activator-inhibitor oscillator, which leads to the emergence of high-robustness motif—the repressilator with positive auto-regulation, improves the oscillation accuracy in comparison to the topology with only an activator-inhibitor oscillator. These design principles may be applicable to other oscillatory circuits.

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

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.

Temporal Variability in Acoustic Behavior of Snapping Shrimp in the East China Sea and Its Correlation With Ocean Environments

The snapping shrimp sound is known to be a major biological noise source of ocean soundscapes in coastal shallow waters of low and mid-latitudes where sunlight reaches. Several studies have been conducted to understand the activity of snapping shrimp through comparison with surrounding environmental factors. In this paper, we report the analysis of the sound produced by snapping shrimp inhabiting an area where sunlight rarely reaches. The acoustic measurements were taken in May 2015 using two 16-channel vertical line arrays (VLAs) moored at a depth of about 100 m, located ∼100 km southwest of Jeju Island, South Korea, as part of the Shallow-water Acoustic Variability Experiment (SAVEX-15). During the experiment, the underwater soundscape was dominated by the broadband impulsive snapping shrimp noise, which is notable considering that snapping shrimp are commonly observed at very shallow depths of tens of meters or less where sunlight can easily reach. To extract snapping events in the ambient noise data, an envelope correlation combined with an amplitude threshold detection algorithm were applied, and then the sea surface-bounced path was filtered out using a kurtosis value of the waveform to avoid double-counting in snap rate estimates. The analysis of the ambient noise data received for 5 consecutive days indicated that the snap rate fluctuated with a strong one-quarter-diurnal variation between 200 and 1,200 snaps per minute, which is distinguished from the periodicity of the snap rate reported in the euphotic zone. The temporal variation in the snap rate is compared with several environmental factors such as water temperature, tidal level, and current speed. It is found that the snap rate has a significant correlation with the current speed, suggesting that snapping shrimp living in the area with little sunlight might change their snapping behavior in response to changes in current speed.

Dataset-specific thresholds significantly improve detection of low transcribed regulatory genes in polysome profiling experiments

MotivationPolysome profiling is novel, and yet has proved to be an effective approach to detect mRNAs with differential ribosomal load and explore the regulatory mechanisms driving efficient translation. Genes encoding regulatory proteins, having a great influence of the organism, usually reveal moderate to low transcriptional levels, compared, for example, to genes of house-keeping machinery. This complicates the reliable detection of such genes in the presence of technical and/or biological noise.ResultsIn this work we investigate how cleaning of polysome profiling data on Arabidopsis thaliana influences the ability to detect genes with low level of total mRNA, but with a highly differential ribosomal load, i.e. genes translationally active. Suggested data modelling approach to identify a background level of mRNA counts individually for each dataset, shows higher power in detection of low transcribed genes, compared to the use of thresholds for the minimal required mRNA counts or the use of raw data. The significant increase in detected number of regulation–related genes was demonstrated. The described approach is applicable to a wide variety of RNA-seq data. All identified and classified mRNAs with high and low translation status are made available in supplementary material.

Analysis of Biological Noise in an Organelle Size Control System

Analysis of fluctuation in organelle size provides a new way to probe the mechanisms of organelle size control systems. By analyzing cell-to-cell variation and within-cell fluctuations of flagellar length in Chlamydomonas, we show that the flagellar length control system exhibits both types of variation. Cell to cell variation is dominated by cell size, while within-cell variation results from dynamic fluctuations that are subject to a constraint, providing evidence for a homeostatic size control system. We analyzed a series of candidate genes affecting flagella and found that flagellar length variation is increased in mutations which increase the average flagellar length, an effect that we show is consistent with a theoretical model for flagellar length regulation based on length-dependent intraflagellar transport balanced by length-independent disassembly. Comparing the magnitude and time-scale of length fluctuations with simple models suggests that tubulin assembly is not directly coupled with IFT-mediated arrival and that observed fluctuations involve tubulin assembly and disassembly events involving large numbers of tubulin dimers. Cells with greater differences in their flagellar lengths show impaired swimming but improved gliding motility, raising the possibility that cells have evolved mechanisms to tune intrinsic noise in length. Taken together our results show that biological noise exists at the level of subcellular structures, with a corresponding effect on cell function, and can provide new insights into the mechanisms of organelle size control.

Coordination between patterning and morphogenesis ensures robustness during mouse development

The mammalian preimplantation embryo is a highly tractable, self-organizing developmental system in which three cell types are consistently specified without the need for maternal factors or external signals. Studies in the mouse over the past decades have greatly improved our understanding of the cues that trigger symmetry breaking in the embryo, the transcription factors that control lineage specification and commitment, and the mechanical forces that drive morphogenesis and inform cell fate decisions. These studies have also uncovered how these multiple inputs are integrated to allocate the right number of cells to each lineage despite inherent biological noise, and as a response to perturbations. In this review, we summarize our current understanding of how these processes are coordinated to ensure a robust and precise developmental outcome during early mouse development. This article is part of a discussion meeting issue ‘Contemporary morphogenesis'.

Leading edge stability in motile cells is an emergent property of branched actin network growth

Animal cell migration is predominantly driven by the coordinated, yet stochastic, polymerization of thousands of nanometer-scale actin filaments across micron-scale cell leading edges. It remains unclear how such inherently noisy processes generate robust cellular behavior. We employed high-speed, high-resolution imaging of migrating neutrophil-like HL-60 cells to explore the fine-scale dynamic shape fluctuations that emerge and relax throughout the process of leading edge maintenance. We then developed a minimal stochastic model of the leading edge that is able to reproduce this stable relaxation behavior. Remarkably, we find that lamellipodial stability naturally emerges from the interplay between branched actin network growth and leading edge shape – with no additional feedback required – based on a synergy between membrane-proximal branching and lateral spreading of filaments. These results thus demonstrate a novel biological noise-suppression mechanism based entirely on system geometry. Furthermore, our model suggests that the Arp2/3-mediated ∼70-80º branching angle optimally smooths lamellipodial shape, addressing its long-mysterious conservation from protists to mammals.One sentence summaryAn experimental and computational investigation of fluctuation dynamics at the leading edge of motile cells demonstrates that the specific angular geometry of Arp2/3-mediated actin network branch formation lies at the core of a successful biological noise-suppression strategy.