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

DOI10.1515/SAGMB-2016-0002MaRDI QIDQ523919zbMATH OpenOpenAlexWikidataFDO

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)

Full work available at URL https://arxiv.org/abs/1601.03334, http://europepmc.org/articles/pmc5518956

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)

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.

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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)

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

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