Estimating intrinsic and extrinsic noise from single-cell gene expression measurements

DOI10.1515/SAGMB-2016-0002zbMATH Open1360.92008OpenAlexW2963583236WikidataQ39163538 ScholiaQ39163538MaRDI QIDQ523919FDOQ523919

Authors: Audrey Qiuyan Fu, Lior Pachter 

Publication date: 25 April 2017

Published in: Statistical Applications in Genetics and Molecular Biology (Search for Journal in Brave)

Abstract: Gene expression is stochastic and displays variation ("noise") both within and between cells. Intracellular (intrinsic) variance can be distinguished from extracellular (extrinsic) variance by applying the law of total variance to data from two-reporter assays that probe expression of identical gene pairs in single-cells. We examine established formulas for the estimation of intrinsic and extrinsic noise and provide interpretations of them in terms of a hierarchical model. This allows us to derive corrections that minimize the mean squared error, an objective that may be important when sample sizes are small. The statistical framework also highlights the need for quantile normalization, and provides justification for the use of the sample correlation between the two reporter expression levels to estimate the percent contribution of extrinsic noise to the total noise. Finally, we provide a geometric interpretation of these results that clarifies the current interpretation.

Full work available at URL: https://arxiv.org/abs/1601.03334

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zbMATH Keywords

noisegene expressionoptimal estimatorssingle cell

Mathematics Subject Classification ID

Applications of statistics to biology and medical sciences; meta analysis (62P10) General biostatistics (92B15) Biochemistry, molecular biology (92C40)

Cites Work

• A geometrical interpretation of an alternative formula for the sample covariance
• Accounting for extrinsic variability in the estimation of stochastic rate constants
• Estimation with quadratic loss.
• Quantifying intrinsic and extrinsic noise in gene transcription using the linear noise approximation: an application to single cell data

Cited In (10)

• Accounting for extrinsic variability in the estimation of stochastic rate constants
• Quantifying intrinsic and extrinsic noise in gene transcription using the linear noise approximation: an application to single cell data
• On observability and reconstruction of promoter activity statistics from reporter protein mean and variance profiles
• Reconstructing statistics of promoter switching from reporter protein population snapshot data
• A common repressor pool results in indeterminacy of extrinsic noise
• Data denoising and post-denoising corrections in single cell RNA sequencing
• Quantitative noise analysis for gene expression microarray experiments
• A structured population modeling framework for quantifying and predicting gene expression noise in flow cytometry data
• Noise correction in gene expression data: a new approach based on subspace method
• Noise and delay can shape distribution functions in stochastic reaction dynamics

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