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Sequencing technology does not eliminate biological variability

Nature Biotechnology volume 29, pages 572–573 (2011)Cite this article

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To the Editor:

RNA sequencing technology provides various advantages over DNA microarrays. For example, it is possible to measure alternative transcription1 or measure transcription for noncoding regions2 de novo. Another potential advantage is low technical variation2,3,4. This has led to rapid adoption of the technology and a recent surge of publications5. We would like to caution, however, that the euphoria surrounding the technology has led many of these publications to discount the influence of biological variability, forgetting perhaps that unwanted variability in gene expression measurements is not due only to measurement error. Gene expression is a stochastic process6 and is known to vary between units considered to be of the same population, for example, in samples from a specific healthy tissue across individuals7. In a typical experiment, variation in gene expression measurements [Var(Expr)] can be decomposed8 as the following:

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Figure 1: Biological variability measured with sequencing and microarrays.

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Authors and Affiliations

  1. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

    Kasper D Hansen, Rafael A Irizarry & Jeffrey T Leek

  2. Department of Community Health, Section of Biostatistics, Brown University, Providence, Rhode Island, USA

    Zhijin Wu

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  1. Kasper D Hansen
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  2. Zhijin Wu
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  3. Rafael A Irizarry
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  4. Jeffrey T Leek
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Correspondence to Rafael A Irizarry or Jeffrey T Leek.

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Supplementary Figures 1 and 2, Supplementary Table 1 and Supplementary Methods (PDF 1512 kb)

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Hansen, K., Wu, Z., Irizarry, R. et al. Sequencing technology does not eliminate biological variability. Nat Biotechnol 29, 572–573 (2011). https://doi.org/10.1038/nbt.1910

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