Limits...
Modularity and predictability in cell signaling and decision making.

Atay O, Skotheim JM - Mol. Biol. Cell (2014)

Bottom Line: Even within a genetically identical population of cells grown in the same environment, cell-to-cell variations in mRNA and protein concentrations can be as high as 50% in yeast and even higher in mammalian cells.Here we discuss the implications of recent advances in genomics, single-cell, and single-cell genomics technology for network modularity and cellular decisions.On the basis of these recent advances, we argue that most gene expression stochasticity and pathway interconnectivity is nonfunctional and that cellular decisions are likely much more predictable than previously expected.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Stanford University, Stanford, CA 94305.

Show MeSH

Related in: MedlinePlus

Hierarchies of organization from network to pathway to motifs. (A) In the network view, pathways are usually not readily discernible because of many apparent interactions between pathways from genomic studies (the pathway in question similarly colored in all panels). We note that in many network analyses, there is no information about the functional significance of interactions. (B) Even though the identity of components (receptors, kinases, transcription factors, downstream targets) is usually indicated in the pathway view, it is a static description of a dynamic system. (C) The separation of time scales may allow the analysis of groups of network components as functionally distinct motifs. The example shown here is idealized because for most pathways; not all components can be so easily broken down into motifs. In this example, “fast” indicates the phosphorylation time scale (∼1 min), and “slow” signifies transcription time scale (∼15 min to 1 h) typical of yeast.
© Copyright Policy - creative-commons
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4230600&req=5

Figure 1: Hierarchies of organization from network to pathway to motifs. (A) In the network view, pathways are usually not readily discernible because of many apparent interactions between pathways from genomic studies (the pathway in question similarly colored in all panels). We note that in many network analyses, there is no information about the functional significance of interactions. (B) Even though the identity of components (receptors, kinases, transcription factors, downstream targets) is usually indicated in the pathway view, it is a static description of a dynamic system. (C) The separation of time scales may allow the analysis of groups of network components as functionally distinct motifs. The example shown here is idealized because for most pathways; not all components can be so easily broken down into motifs. In this example, “fast” indicates the phosphorylation time scale (∼1 min), and “slow” signifies transcription time scale (∼15 min to 1 h) typical of yeast.

Mentions: Moreover, it is likely that there are additional hierarchies of organization from network to pathway to even smaller groups of signaling molecules known as motifs (Figure 1). This hierarchical organization is in part due to the separate time scales of biological interactions. For instance, phosphorylation reactions are very fast, whereas protein synthesis and corresponding concentration changes are relatively slow. This allows analysis of phosphorylation kinetics of a few pathway components comprising a motif while treating protein concentrations as fixed. Thus the motif's dynamics can be studied in depth, and its function can be characterized. Indeed, motif analysis has made great progress in determining signaling principles (Alon, 2007), suggesting a view of biology as tractable, modular on several scales, and, it is hoped, ultimately predictable. According to this view, with sufficient understanding of networks and signaling principles, we should be able to understand how cells process information and predict what the output of a cellular decision will be from the measurements of regulatory proteins.


Modularity and predictability in cell signaling and decision making.

Atay O, Skotheim JM - Mol. Biol. Cell (2014)

Hierarchies of organization from network to pathway to motifs. (A) In the network view, pathways are usually not readily discernible because of many apparent interactions between pathways from genomic studies (the pathway in question similarly colored in all panels). We note that in many network analyses, there is no information about the functional significance of interactions. (B) Even though the identity of components (receptors, kinases, transcription factors, downstream targets) is usually indicated in the pathway view, it is a static description of a dynamic system. (C) The separation of time scales may allow the analysis of groups of network components as functionally distinct motifs. The example shown here is idealized because for most pathways; not all components can be so easily broken down into motifs. In this example, “fast” indicates the phosphorylation time scale (∼1 min), and “slow” signifies transcription time scale (∼15 min to 1 h) typical of yeast.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230600&req=5

Figure 1: Hierarchies of organization from network to pathway to motifs. (A) In the network view, pathways are usually not readily discernible because of many apparent interactions between pathways from genomic studies (the pathway in question similarly colored in all panels). We note that in many network analyses, there is no information about the functional significance of interactions. (B) Even though the identity of components (receptors, kinases, transcription factors, downstream targets) is usually indicated in the pathway view, it is a static description of a dynamic system. (C) The separation of time scales may allow the analysis of groups of network components as functionally distinct motifs. The example shown here is idealized because for most pathways; not all components can be so easily broken down into motifs. In this example, “fast” indicates the phosphorylation time scale (∼1 min), and “slow” signifies transcription time scale (∼15 min to 1 h) typical of yeast.
Mentions: Moreover, it is likely that there are additional hierarchies of organization from network to pathway to even smaller groups of signaling molecules known as motifs (Figure 1). This hierarchical organization is in part due to the separate time scales of biological interactions. For instance, phosphorylation reactions are very fast, whereas protein synthesis and corresponding concentration changes are relatively slow. This allows analysis of phosphorylation kinetics of a few pathway components comprising a motif while treating protein concentrations as fixed. Thus the motif's dynamics can be studied in depth, and its function can be characterized. Indeed, motif analysis has made great progress in determining signaling principles (Alon, 2007), suggesting a view of biology as tractable, modular on several scales, and, it is hoped, ultimately predictable. According to this view, with sufficient understanding of networks and signaling principles, we should be able to understand how cells process information and predict what the output of a cellular decision will be from the measurements of regulatory proteins.

Bottom Line: Even within a genetically identical population of cells grown in the same environment, cell-to-cell variations in mRNA and protein concentrations can be as high as 50% in yeast and even higher in mammalian cells.Here we discuss the implications of recent advances in genomics, single-cell, and single-cell genomics technology for network modularity and cellular decisions.On the basis of these recent advances, we argue that most gene expression stochasticity and pathway interconnectivity is nonfunctional and that cellular decisions are likely much more predictable than previously expected.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Stanford University, Stanford, CA 94305.

Show MeSH
Related in: MedlinePlus