Dataset Information

Quantifying Stochastic Noise in Cultured Circadian Reporter Cells.

ABSTRACT: Stochastic noise at the cellular level has been shown to play a fundamental role in circadian oscillations, influencing how groups of cells entrain to external cues and likely serving as the mechanism by which cell-autonomous rhythms are generated. Despite this importance, few studies have investigated how clock perturbations affect stochastic noise-even as increasing numbers of high-throughput screens categorize how gene knockdowns or small molecules can change clock period and amplitude. This absence is likely due to the difficulty associated with measuring cell-autonomous stochastic noise directly, which currently requires the careful collection and processing of single-cell data. In this study, we show that the damping rate of population-level bioluminescence recordings can serve as an accurate measure of overall stochastic noise, and one that can be applied to future and existing high-throughput circadian screens. Using cell-autonomous fibroblast data, we first show directly that higher noise at the single-cell results in faster damping at the population level. Next, we show that the damping rate of cultured cells can be changed in a dose-dependent fashion by small molecule modulators, and confirm that such a change can be explained by single-cell noise using a mathematical model. We further demonstrate the insights that can be gained by applying our method to a genome-wide siRNA screen, revealing that stochastic noise is altered independently from period, amplitude, and phase. Finally, we hypothesize that the unperturbed clock is highly optimized for robust rhythms, as very few gene perturbations are capable of simultaneously increasing amplitude and lowering stochastic noise. Ultimately, this study demonstrates the importance of considering the effect of circadian perturbations on stochastic noise, particularly with regard to the development of small-molecule circadian therapeutics.

SUBMITTER: St John PC

PROVIDER: S-EPMC4654518 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Quantifying Stochastic Noise in Cultured Circadian Reporter Cells.

St John Peter C PC Doyle Francis J FJ

PLoS computational biology 20151120 11

Stochastic noise at the cellular level has been shown to play a fundamental role in circadian oscillations, influencing how groups of cells entrain to external cues and likely serving as the mechanism by which cell-autonomous rhythms are generated. Despite this importance, few studies have investigated how clock perturbations affect stochastic noise-even as increasing numbers of high-throughput screens categorize how gene knockdowns or small molecules can change clock period and amplitude. This ...[more]

PMID: 26588000

Similar Datasets

Project description:BACKGROUND:Exposure to both occupational and nonoccupational noise is recognized as a risk factor for noise-induced hearing loss (NIHL). Although audiologists routinely inquire regarding history of noise exposure, there are limited tools available for quantifying this history or for identifying those individuals who are at highest risk for NIHL. Identifying those at highest risk would allow hearing conservation activities to be focused on those individuals. PURPOSE:To develop a detailed, task-based questionnaire for quantifying an individual's annual noise exposure (ANE) arising from both occupational and nonoccupational sources (aim 1) and to develop a short screening tool that could be used to identify individuals at high risk of NIHL (aim 2). RESEARCH DESIGN:Review of relevant literature for questionnaire development followed by a cross-sectional descriptive and correlational investigation of the newly developed questionnaire and screening tool. STUDY SAMPLE:One hundred fourteen college freshmen completed the detailed questionnaire for estimating ANE (aim 1) and answered the potential screening questions (aim 2). An additional 59 adults participated in data collection where the accuracy of the screening tool was evaluated (aim 2). DATA COLLECTION AND ANALYSIS:In study aim 1, all participants completed the detailed questionnaire and the potential screening questions. Descriptive statistics were used to quantify participant participation in various noisy activities and their associated ANE estimates. In study aim 2, linear regression techniques were used to identify screening questions that could be used to predict a participant's estimated ANE. Clinical decision theory was then used to assess the accuracy with which the screening tool predicted high and low risk of NIHL in a new group of participants. RESULTS:Responses on the detailed questionnaire indicated that our sample of college freshmen reported high rates of participation in a variety of occupational and nonoccupational activities associated with high sound levels. Although participation rates were high, ANE estimates were below highest-risk levels for many participants because the frequency of participation in these activities was low in many cases. These data illustrate how the Noise Exposure Questionnaire (NEQ) could be used to provide detailed and specific information regarding an individual's exposure to noise. The results of aim 2 suggest that the screening tool, the 1-Minute Noise Screen, can be used to identify those participants with high- and low-risk noise exposure, allowing more in-depth assessment of noise exposure history to be targeted at those most at risk. CONCLUSIONS:The NEQ can be used to estimate an individual's ANE and the 1-Minute Noise Screen can be used to identify those participants at highest risk of NIHL. These tools allow audiologists to focus hearing conservation efforts on those individuals who are most in need of those services.

Dataset Information

Quantifying Stochastic Noise in Cultured Circadian Reporter Cells.

Publications

Quantifying Stochastic Noise in Cultured Circadian Reporter Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets