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Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks.

Albergante L, Blow JJ, Newman TJ - Elife (2014)

Bottom Line: The gene regulatory network (GRN) is the central decision-making module of the cell.BQS explains many of the small- and large-scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response.BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom l.albergante@dundee.ac.uk.

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Long feedback loops in Lee et al. (yeast).Only one long feedback loop is observed in the yeast dataset derived by Lee et al. (A). Since Harbison et al. (2004) uses a technology similar to Lee et al. (2002) and can be considered to have provided an updated version of the network, we analysed what caused the disappearance of the invalid loop reported by Lee et al. (2002). Five of the six interactions have comparable p-values in the two datasets (A and B). However, the p-value for the interaction between ROX1 and YAP6 changes by three orders of magnitude, thus transforming the feedback loop into a feedforward loop that is consistent with BQS. This observation indicates how the strong predictions of BQS can be used to identify potential inaccuracies and problems in GRN data.DOI:http://dx.doi.org/10.7554/eLife.02863.028
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fig6s3: Long feedback loops in Lee et al. (yeast).Only one long feedback loop is observed in the yeast dataset derived by Lee et al. (A). Since Harbison et al. (2004) uses a technology similar to Lee et al. (2002) and can be considered to have provided an updated version of the network, we analysed what caused the disappearance of the invalid loop reported by Lee et al. (2002). Five of the six interactions have comparable p-values in the two datasets (A and B). However, the p-value for the interaction between ROX1 and YAP6 changes by three orders of magnitude, thus transforming the feedback loop into a feedforward loop that is consistent with BQS. This observation indicates how the strong predictions of BQS can be used to identify potential inaccuracies and problems in GRN data.DOI:http://dx.doi.org/10.7554/eLife.02863.028

Mentions: P. aeruginosa has no long (>3 genes) feedback loops, and of its seven 2-node feedback loops five are isolated, and so are either stable or likely to act as switches, whilst the other two are linked but are of a form (positive-negative) that makes them Qualitatively Stable. Both of the S. cerevisiae 2-node feedback loops are isolated, whilst the human GM12878 cell line has only a single 2-node feedback loop which is therefore isolated. Curiously, the only long feedback loop observed in the yeast GRN derived by Lee et al. (2002) presents the same potentially chaotic topology discussed above. However, this illegal motif is not present in the more recent GRN derived by Harbison et al. (2004) (Figure 6—figure supplement 3).


Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks.

Albergante L, Blow JJ, Newman TJ - Elife (2014)

Long feedback loops in Lee et al. (yeast).Only one long feedback loop is observed in the yeast dataset derived by Lee et al. (A). Since Harbison et al. (2004) uses a technology similar to Lee et al. (2002) and can be considered to have provided an updated version of the network, we analysed what caused the disappearance of the invalid loop reported by Lee et al. (2002). Five of the six interactions have comparable p-values in the two datasets (A and B). However, the p-value for the interaction between ROX1 and YAP6 changes by three orders of magnitude, thus transforming the feedback loop into a feedforward loop that is consistent with BQS. This observation indicates how the strong predictions of BQS can be used to identify potential inaccuracies and problems in GRN data.DOI:http://dx.doi.org/10.7554/eLife.02863.028
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151086&req=5

fig6s3: Long feedback loops in Lee et al. (yeast).Only one long feedback loop is observed in the yeast dataset derived by Lee et al. (A). Since Harbison et al. (2004) uses a technology similar to Lee et al. (2002) and can be considered to have provided an updated version of the network, we analysed what caused the disappearance of the invalid loop reported by Lee et al. (2002). Five of the six interactions have comparable p-values in the two datasets (A and B). However, the p-value for the interaction between ROX1 and YAP6 changes by three orders of magnitude, thus transforming the feedback loop into a feedforward loop that is consistent with BQS. This observation indicates how the strong predictions of BQS can be used to identify potential inaccuracies and problems in GRN data.DOI:http://dx.doi.org/10.7554/eLife.02863.028
Mentions: P. aeruginosa has no long (>3 genes) feedback loops, and of its seven 2-node feedback loops five are isolated, and so are either stable or likely to act as switches, whilst the other two are linked but are of a form (positive-negative) that makes them Qualitatively Stable. Both of the S. cerevisiae 2-node feedback loops are isolated, whilst the human GM12878 cell line has only a single 2-node feedback loop which is therefore isolated. Curiously, the only long feedback loop observed in the yeast GRN derived by Lee et al. (2002) presents the same potentially chaotic topology discussed above. However, this illegal motif is not present in the more recent GRN derived by Harbison et al. (2004) (Figure 6—figure supplement 3).

Bottom Line: The gene regulatory network (GRN) is the central decision-making module of the cell.BQS explains many of the small- and large-scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response.BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation.

View Article: PubMed Central - PubMed

Affiliation: College of Life Sciences, University of Dundee, Dundee, United Kingdom l.albergante@dundee.ac.uk.

Show MeSH
Related in: MedlinePlus