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Quantifying epistatic interactions among the components constituting the protein translation system.

Matsuura T, Kazuta Y, Aita T, Adachi J, Yomo T - Mol. Syst. Biol. (2009)

Bottom Line: Analyses of the data measured using various combinations of component concentrations indicated that the contributions of larger than 2-body inter-component epistatic interactions are negligible, despite the presence of larger than 2-body physical interactions.These findings allowed the prediction of protein synthesis activity at various combinations of component concentrations from a small number of samples, the principle of which is applicable to analysis and optimization of other biological systems.Moreover, the average ratio of 2- to 1-body terms was estimated to be as small as 0.1, implying high adaptability and evolvability of the protein translation system.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics Engineering, Graduate School of Information Science and Technology, Osaka University, Suita, Osaka, Japan.

ABSTRACT
In principle, the accumulation of knowledge regarding the molecular basis of biological systems should allow the development of large-scale kinetic models of their functions. However, the development of such models requires vast numbers of parameters, which are difficult to obtain in practice. Here, we used an in vitro translation system, consisting of 69 defined components, to quantify the epistatic interactions among changes in component concentrations through Bahadur expansion, thereby obtaining a coarse-grained model of protein synthesis activity. Analyses of the data measured using various combinations of component concentrations indicated that the contributions of larger than 2-body inter-component epistatic interactions are negligible, despite the presence of larger than 2-body physical interactions. These findings allowed the prediction of protein synthesis activity at various combinations of component concentrations from a small number of samples, the principle of which is applicable to analysis and optimization of other biological systems. Moreover, the average ratio of 2- to 1-body terms was estimated to be as small as 0.1, implying high adaptability and evolvability of the protein translation system.

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Grouping of the 69 components into modules to investigate the inter-module interactions. (A) Three modularization schemes used in this study. The 69 components were grouped into 4 (scheme 1) or 3 modules (schemes 2 and 3). See Supplementary Table S1 for abbreviations of the names of the components and their concentrations. (B) Combinatorial experiments of modules ‘0000 × 1111' (left) and ‘1111 × 2222' (right). Modularization was carried out according to scheme 1. Notations, such as ‘0101', indicate the concentration vector generated by combining the modules (m10, m21, m30, m41). Fluorescence intensities of synthesized GFP for each binary sequence are shown on the vertical axis. Results of two independent trials are shown. (C) Combinatorial experiments using modules ‘000 × 111.' Modularization was carried out according to scheme 2 or 3. Results of two independent trials are shown. Text data of (B) and (C) are given in Supplementary Table S4.
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f2: Grouping of the 69 components into modules to investigate the inter-module interactions. (A) Three modularization schemes used in this study. The 69 components were grouped into 4 (scheme 1) or 3 modules (schemes 2 and 3). See Supplementary Table S1 for abbreviations of the names of the components and their concentrations. (B) Combinatorial experiments of modules ‘0000 × 1111' (left) and ‘1111 × 2222' (right). Modularization was carried out according to scheme 1. Notations, such as ‘0101', indicate the concentration vector generated by combining the modules (m10, m21, m30, m41). Fluorescence intensities of synthesized GFP for each binary sequence are shown on the vertical axis. Results of two independent trials are shown. (C) Combinatorial experiments using modules ‘000 × 111.' Modularization was carried out according to scheme 2 or 3. Results of two independent trials are shown. Text data of (B) and (C) are given in Supplementary Table S4.

Mentions: Box 1 shows a schematic representation of the modularization experiments. We prepared four modules from each of the concentration vectors C0 and C1, according to modularization scheme 1 (Figure 2A), yielding concentration vectors (m1t, m2t, m3t, m4t)=Ct (t=0,1), where mkt is the vector of the component's concentrations given by the modularization scheme. Then, the activity of the system was measured by recombining these modules (Box 1). Notations, such as ‘0000' and ‘1111' in Box 1 indicate (m10, m20, m30, m40) and (m11, m21, m31, m41), respectively. As this ‘sequence' (e.g., ‘0101'=(m10, m21, m30, m41)) gives a set of concentrations of all 69 components, fluorescence intensity is assigned for this sequence. Figure 2B shows the fluorescence intensities of all possible sequences generated by recombining the modules ‘0000' and ‘1111' (denoted as ‘0000 × 1111') (left), where 16 experimental data sets were obtained. Identical experiments were carried out by grouping C1 and C2 into four modules according to modularization scheme 1 (denoted as ‘1111 × 2222') (Figure 2B, right), or by grouping C0 and C1 into three modules according to modularization scheme 2 or 3 (Figure 2A and C) (denoted as ‘000 × 111'). Data shown in Figures 2B and C were subjected to Bahadur expansion analysis to quantify the inter-module interactions.


Quantifying epistatic interactions among the components constituting the protein translation system.

Matsuura T, Kazuta Y, Aita T, Adachi J, Yomo T - Mol. Syst. Biol. (2009)

Grouping of the 69 components into modules to investigate the inter-module interactions. (A) Three modularization schemes used in this study. The 69 components were grouped into 4 (scheme 1) or 3 modules (schemes 2 and 3). See Supplementary Table S1 for abbreviations of the names of the components and their concentrations. (B) Combinatorial experiments of modules ‘0000 × 1111' (left) and ‘1111 × 2222' (right). Modularization was carried out according to scheme 1. Notations, such as ‘0101', indicate the concentration vector generated by combining the modules (m10, m21, m30, m41). Fluorescence intensities of synthesized GFP for each binary sequence are shown on the vertical axis. Results of two independent trials are shown. (C) Combinatorial experiments using modules ‘000 × 111.' Modularization was carried out according to scheme 2 or 3. Results of two independent trials are shown. Text data of (B) and (C) are given in Supplementary Table S4.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2736649&req=5

f2: Grouping of the 69 components into modules to investigate the inter-module interactions. (A) Three modularization schemes used in this study. The 69 components were grouped into 4 (scheme 1) or 3 modules (schemes 2 and 3). See Supplementary Table S1 for abbreviations of the names of the components and their concentrations. (B) Combinatorial experiments of modules ‘0000 × 1111' (left) and ‘1111 × 2222' (right). Modularization was carried out according to scheme 1. Notations, such as ‘0101', indicate the concentration vector generated by combining the modules (m10, m21, m30, m41). Fluorescence intensities of synthesized GFP for each binary sequence are shown on the vertical axis. Results of two independent trials are shown. (C) Combinatorial experiments using modules ‘000 × 111.' Modularization was carried out according to scheme 2 or 3. Results of two independent trials are shown. Text data of (B) and (C) are given in Supplementary Table S4.
Mentions: Box 1 shows a schematic representation of the modularization experiments. We prepared four modules from each of the concentration vectors C0 and C1, according to modularization scheme 1 (Figure 2A), yielding concentration vectors (m1t, m2t, m3t, m4t)=Ct (t=0,1), where mkt is the vector of the component's concentrations given by the modularization scheme. Then, the activity of the system was measured by recombining these modules (Box 1). Notations, such as ‘0000' and ‘1111' in Box 1 indicate (m10, m20, m30, m40) and (m11, m21, m31, m41), respectively. As this ‘sequence' (e.g., ‘0101'=(m10, m21, m30, m41)) gives a set of concentrations of all 69 components, fluorescence intensity is assigned for this sequence. Figure 2B shows the fluorescence intensities of all possible sequences generated by recombining the modules ‘0000' and ‘1111' (denoted as ‘0000 × 1111') (left), where 16 experimental data sets were obtained. Identical experiments were carried out by grouping C1 and C2 into four modules according to modularization scheme 1 (denoted as ‘1111 × 2222') (Figure 2B, right), or by grouping C0 and C1 into three modules according to modularization scheme 2 or 3 (Figure 2A and C) (denoted as ‘000 × 111'). Data shown in Figures 2B and C were subjected to Bahadur expansion analysis to quantify the inter-module interactions.

Bottom Line: Analyses of the data measured using various combinations of component concentrations indicated that the contributions of larger than 2-body inter-component epistatic interactions are negligible, despite the presence of larger than 2-body physical interactions.These findings allowed the prediction of protein synthesis activity at various combinations of component concentrations from a small number of samples, the principle of which is applicable to analysis and optimization of other biological systems.Moreover, the average ratio of 2- to 1-body terms was estimated to be as small as 0.1, implying high adaptability and evolvability of the protein translation system.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics Engineering, Graduate School of Information Science and Technology, Osaka University, Suita, Osaka, Japan.

ABSTRACT
In principle, the accumulation of knowledge regarding the molecular basis of biological systems should allow the development of large-scale kinetic models of their functions. However, the development of such models requires vast numbers of parameters, which are difficult to obtain in practice. Here, we used an in vitro translation system, consisting of 69 defined components, to quantify the epistatic interactions among changes in component concentrations through Bahadur expansion, thereby obtaining a coarse-grained model of protein synthesis activity. Analyses of the data measured using various combinations of component concentrations indicated that the contributions of larger than 2-body inter-component epistatic interactions are negligible, despite the presence of larger than 2-body physical interactions. These findings allowed the prediction of protein synthesis activity at various combinations of component concentrations from a small number of samples, the principle of which is applicable to analysis and optimization of other biological systems. Moreover, the average ratio of 2- to 1-body terms was estimated to be as small as 0.1, implying high adaptability and evolvability of the protein translation system.

Show MeSH
Related in: MedlinePlus