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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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Quantification of inter-component interactions. (A) Six components (Mg(OAc)2, tRNA, spermidine, K-Glu, NTPs, and CP) were designed to take the concentration either in C1 or C2, whereas the concentrations of the other 63 components were fixed to C1 (values are given in Supplementary Table S2). Therefore, the experimental conditions (concentration vector) here can be written as a binary sequence of length 6, for example, ‘111111'=(cMg(OAc))21, ctRNA1, cspermidine1, cK-Glu1, cNTP1, cCP1) and ‘222222'=(cMg(OAc)22, ctRNA2, cspermidine2, cK-Glu2, cNTP2, cCP2). The experimental results of ‘111111 × 222222' are shown. Text data are given in Supplementary Table S4. (B) R2 values calculated by the 1st–6th order truncation of equation (m4) for the combinatorial experiments of six components.
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f4: Quantification of inter-component interactions. (A) Six components (Mg(OAc)2, tRNA, spermidine, K-Glu, NTPs, and CP) were designed to take the concentration either in C1 or C2, whereas the concentrations of the other 63 components were fixed to C1 (values are given in Supplementary Table S2). Therefore, the experimental conditions (concentration vector) here can be written as a binary sequence of length 6, for example, ‘111111'=(cMg(OAc))21, ctRNA1, cspermidine1, cK-Glu1, cNTP1, cCP1) and ‘222222'=(cMg(OAc)22, ctRNA2, cspermidine2, cK-Glu2, cNTP2, cCP2). The experimental results of ‘111111 × 222222' are shown. Text data are given in Supplementary Table S4. (B) R2 values calculated by the 1st–6th order truncation of equation (m4) for the combinatorial experiments of six components.

Mentions: We thus further investigated whether the above conjecture is true by directly measuring the inter-component interactions. We chose six components (magnesium acetate (Mg(OAc)2), transfer RNA (tRNA), spermidine, potassium glutamate (K-Glu), NTPs, and creatine phosphate (CP)), which affected protein synthesis activity when their concentrations were altered. The experiment was designed such that each of the six components took the concentration in either C1 or C2, whereas the concentrations of the remaining 63 components were fixed to C1 (values are given in Supplementary Table S2). Therefore, the experimental conditions here can be written as a binary sequence of length six: for example, ‘111111'=(cMg(OAc)21, ctRNA1, cspermidine1, cK-Glu1, cNTP1, cCP1) and ‘222222'=(cMg(OAc)22, ctRNA2, cspermidine2, cK-Glu2, cNTP2, cCP2). The results of ‘111111 × 222222' are shown in Figure 4A. R2 values calculated using the 1st–6th order truncation are shown in Figure 4B. The R2 value reached more than 0.99 even without coefficients higher than 2nd order, indicating that 2nd order truncation is sufficient to explain the experimental results. These results were consistent with the conjecture, further suggesting that the above conjecture is true.


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)

Quantification of inter-component interactions. (A) Six components (Mg(OAc)2, tRNA, spermidine, K-Glu, NTPs, and CP) were designed to take the concentration either in C1 or C2, whereas the concentrations of the other 63 components were fixed to C1 (values are given in Supplementary Table S2). Therefore, the experimental conditions (concentration vector) here can be written as a binary sequence of length 6, for example, ‘111111'=(cMg(OAc))21, ctRNA1, cspermidine1, cK-Glu1, cNTP1, cCP1) and ‘222222'=(cMg(OAc)22, ctRNA2, cspermidine2, cK-Glu2, cNTP2, cCP2). The experimental results of ‘111111 × 222222' are shown. Text data are given in Supplementary Table S4. (B) R2 values calculated by the 1st–6th order truncation of equation (m4) for the combinatorial experiments of six components.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Quantification of inter-component interactions. (A) Six components (Mg(OAc)2, tRNA, spermidine, K-Glu, NTPs, and CP) were designed to take the concentration either in C1 or C2, whereas the concentrations of the other 63 components were fixed to C1 (values are given in Supplementary Table S2). Therefore, the experimental conditions (concentration vector) here can be written as a binary sequence of length 6, for example, ‘111111'=(cMg(OAc))21, ctRNA1, cspermidine1, cK-Glu1, cNTP1, cCP1) and ‘222222'=(cMg(OAc)22, ctRNA2, cspermidine2, cK-Glu2, cNTP2, cCP2). The experimental results of ‘111111 × 222222' are shown. Text data are given in Supplementary Table S4. (B) R2 values calculated by the 1st–6th order truncation of equation (m4) for the combinatorial experiments of six components.
Mentions: We thus further investigated whether the above conjecture is true by directly measuring the inter-component interactions. We chose six components (magnesium acetate (Mg(OAc)2), transfer RNA (tRNA), spermidine, potassium glutamate (K-Glu), NTPs, and creatine phosphate (CP)), which affected protein synthesis activity when their concentrations were altered. The experiment was designed such that each of the six components took the concentration in either C1 or C2, whereas the concentrations of the remaining 63 components were fixed to C1 (values are given in Supplementary Table S2). Therefore, the experimental conditions here can be written as a binary sequence of length six: for example, ‘111111'=(cMg(OAc)21, ctRNA1, cspermidine1, cK-Glu1, cNTP1, cCP1) and ‘222222'=(cMg(OAc)22, ctRNA2, cspermidine2, cK-Glu2, cNTP2, cCP2). The results of ‘111111 × 222222' are shown in Figure 4A. R2 values calculated using the 1st–6th order truncation are shown in Figure 4B. The R2 value reached more than 0.99 even without coefficients higher than 2nd order, indicating that 2nd order truncation is sufficient to explain the experimental results. These results were consistent with the conjecture, further suggesting that the above conjecture is true.

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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