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Let the data speak

Nature Reviews Molecular Cell Biology volume 7, pages 1–2 (2006)Cite this article

We respectfully contest the contradictory criticisms of Lloyd and Murray. These two scientists have collaborated on studies of short-period metabolic oscillations using the IFO0233 strain of Saccharomyces cerevisiae (τ (period) = 40 min). Lloyd claims that the long-period oscillations described and investigated in our studies using the CEN.PK strain of S. cerevisiae (τ = 4–5 h) are both flawed and fundamentally different from their short-period ultradian oscillations. By contrast, Murray states that the two systems “have clear similarities”. This text articulates our response to the belittling criticisms of Lloyd and Murray.

In evaluating the expression data from the two studies, what are the criteria that can be used to justify oscillatory gene expression matching the period of the observed fluctuation in oxygen consumption? We offer that the only scientifically sound approach to compare and contrast the data sets is unbiased statistical analysis. To this end, we have calculated periodicities of gene expression during our long-period oscillations using both Fourier transform analysis (Lomb periodogram) and our previously described autocorrelation-based statistical methods1 (Table 1). The Fourier analysis shows that at a P-value of 0.0001, an exceptionally rigid metric, there are 678 genes that display a precise, oscillatory periodicity of 300 min, matching the period of rhythmically fluctuating oxygen consumption. If relaxed to P-values of 0.001 or 0.01, unbiased statistical assessment of our data set reveals, respectively, either 1,413 or 2,285 periodically expressed genes. These data formed the basis of our evaluation of the transcriptional logic of the yeast metabolic cycle, leading to the description of a cycle with three phases (oxidative; reductive, building; and reductive, charging).

Table 1 Number of periodic genes at selected significance levels as determined by Fourier (Lomb periodogram) or autocorrelation analysis
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Figure 1: A comparison of phases between sets of the most periodic genes as determined by Fourier analysis (P-value <0.001, 112 genes plotted).
Figure 2: A direct comparison of individual transcript profiles between the long-period and short-period expression data sets.

References

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Authors and Affiliations

  1. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, 75390, Texas, USA

    Benjamin P. Tu, Andrzej Kudlicki, Maga Rowicka & Steven L. McKnight

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  1. Benjamin P. Tu
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  2. Andrzej Kudlicki
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  3. Maga Rowicka
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  4. Steven L. McKnight
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Correspondence to Steven L. McKnight.

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Tu, B., Kudlicki, A., Rowicka, M. et al. Let the data speak. Nat Rev Mol Cell Biol 7, 1–2 (2006). https://doi.org/10.1038/nrm1980-c3

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