Limits...
Circular reasoning rather than cyclic expression.

Jensen LJ, de Lichtenberg U, Jensen TS, Brunak S, Bork P - Genome Biol. (2008)

Bottom Line: A response to Combined analysis reveals a core set of cycling genes by Y Lu, S Mahony, PV Benos, R Rosenfeld, I Simon, LL Breeden and Z Bar-Joseph.Genome Biol 2007, 8:R146.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
A response to Combined analysis reveals a core set of cycling genes by Y Lu, S Mahony, PV Benos, R Rosenfeld, I Simon, LL Breeden and Z Bar-Joseph. Genome Biol 2007, 8:R146.

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Expression values for MCM6 in humans, budding yeast, and fission yeast. Values are log ratios between synchronized and unsynchronized cells. (a, b) Expression profiles of budding yeast MCM6 under different cell-cycle arrest methods [2,3]. (c, d) Expression of fission yeast mcm6 under different arrest methods [4,5]. (e) Expression of MCM6 in human HeLa cells [7]. Cell-cycle stages are shown underneath each panel. Jensen et al. [14] claim that although human MCM6 is cycling at the transcriptional level, its homologs in budding yeast and fission yeast do not cycle. As (a-d) show, the expression of yeast MCM6 seems more cyclic than that of human MCM6, highlighting the limitations of species-by-species thresholding.
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Figure 2: Expression values for MCM6 in humans, budding yeast, and fission yeast. Values are log ratios between synchronized and unsynchronized cells. (a, b) Expression profiles of budding yeast MCM6 under different cell-cycle arrest methods [2,3]. (c, d) Expression of fission yeast mcm6 under different arrest methods [4,5]. (e) Expression of MCM6 in human HeLa cells [7]. Cell-cycle stages are shown underneath each panel. Jensen et al. [14] claim that although human MCM6 is cycling at the transcriptional level, its homologs in budding yeast and fission yeast do not cycle. As (a-d) show, the expression of yeast MCM6 seems more cyclic than that of human MCM6, highlighting the limitations of species-by-species thresholding.

Mentions: Despite claims to the contrary from Jensen et al., previous analyses of cell-cycle expression data resulted in opposing views regarding the conservation of expression between different species. While some investigators have concluded that this conservation is surprisingly low [4,14], others have determined that it is rather large. For example, Oliva et al. [6] found that more than 30% of top cycling genes in budding and fission yeast are cycling and conserved in both species, and Ota et al. [10] identified more than 15% of cycling human genes as cycling and conserved in plants and yeast. The major reason for this discrepancy seems to be the use of strict thresholding for determining whether a gene is cycling or not. Such an analysis on a species-by-species basis may lead to inconsistencies in cell-cycle assignments. Figure 2 of this Correspondence exemplifies this difficulty. While only expression of the human Mcm6 gene was determined to be cycling by Jensen et al. [14], as Figure 2 shows, its curated homologs in budding and fission yeast (which were annotated as non-cycling by Jensen et al.) actually display strong cyclic expression patterns. This is a general problem with cell-cycle analysis. As Figure 3 shows, while some orthologs of cycling budding-yeast genes may fall just below the fission-yeast threshold, they are still (at least weakly) cycling, significantly more than expected by chance, indicating that expression is conserved at a stronger rate than the rate determined by thresholding. To address these issues, we have developed a new method for combining expression data from multiple species [9]. Using our method we concluded that cell-cycle expression is conserved at much higher rates than those claimed by Jensen et al. [14].


Circular reasoning rather than cyclic expression.

Jensen LJ, de Lichtenberg U, Jensen TS, Brunak S, Bork P - Genome Biol. (2008)

Expression values for MCM6 in humans, budding yeast, and fission yeast. Values are log ratios between synchronized and unsynchronized cells. (a, b) Expression profiles of budding yeast MCM6 under different cell-cycle arrest methods [2,3]. (c, d) Expression of fission yeast mcm6 under different arrest methods [4,5]. (e) Expression of MCM6 in human HeLa cells [7]. Cell-cycle stages are shown underneath each panel. Jensen et al. [14] claim that although human MCM6 is cycling at the transcriptional level, its homologs in budding yeast and fission yeast do not cycle. As (a-d) show, the expression of yeast MCM6 seems more cyclic than that of human MCM6, highlighting the limitations of species-by-species thresholding.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2481420&req=5

Figure 2: Expression values for MCM6 in humans, budding yeast, and fission yeast. Values are log ratios between synchronized and unsynchronized cells. (a, b) Expression profiles of budding yeast MCM6 under different cell-cycle arrest methods [2,3]. (c, d) Expression of fission yeast mcm6 under different arrest methods [4,5]. (e) Expression of MCM6 in human HeLa cells [7]. Cell-cycle stages are shown underneath each panel. Jensen et al. [14] claim that although human MCM6 is cycling at the transcriptional level, its homologs in budding yeast and fission yeast do not cycle. As (a-d) show, the expression of yeast MCM6 seems more cyclic than that of human MCM6, highlighting the limitations of species-by-species thresholding.
Mentions: Despite claims to the contrary from Jensen et al., previous analyses of cell-cycle expression data resulted in opposing views regarding the conservation of expression between different species. While some investigators have concluded that this conservation is surprisingly low [4,14], others have determined that it is rather large. For example, Oliva et al. [6] found that more than 30% of top cycling genes in budding and fission yeast are cycling and conserved in both species, and Ota et al. [10] identified more than 15% of cycling human genes as cycling and conserved in plants and yeast. The major reason for this discrepancy seems to be the use of strict thresholding for determining whether a gene is cycling or not. Such an analysis on a species-by-species basis may lead to inconsistencies in cell-cycle assignments. Figure 2 of this Correspondence exemplifies this difficulty. While only expression of the human Mcm6 gene was determined to be cycling by Jensen et al. [14], as Figure 2 shows, its curated homologs in budding and fission yeast (which were annotated as non-cycling by Jensen et al.) actually display strong cyclic expression patterns. This is a general problem with cell-cycle analysis. As Figure 3 shows, while some orthologs of cycling budding-yeast genes may fall just below the fission-yeast threshold, they are still (at least weakly) cycling, significantly more than expected by chance, indicating that expression is conserved at a stronger rate than the rate determined by thresholding. To address these issues, we have developed a new method for combining expression data from multiple species [9]. Using our method we concluded that cell-cycle expression is conserved at much higher rates than those claimed by Jensen et al. [14].

Bottom Line: A response to Combined analysis reveals a core set of cycling genes by Y Lu, S Mahony, PV Benos, R Rosenfeld, I Simon, LL Breeden and Z Bar-Joseph.Genome Biol 2007, 8:R146.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
A response to Combined analysis reveals a core set of cycling genes by Y Lu, S Mahony, PV Benos, R Rosenfeld, I Simon, LL Breeden and Z Bar-Joseph. Genome Biol 2007, 8:R146.

Show MeSH
Related in: MedlinePlus