skip to main content
Ngôn ngữ:
Giới hạn tìm kiếm: Giới hạn tìm kiếm: Dạng tài nguyên Hiển thị kết quả với: Hiển thị kết quả với: Chỉ mục

Optimization of Time-Course Experiments for Kinetic Model Discrimination (Kinetic Model Discrimination)

Lages, Nuno F ; Cordeiro, Carlos ; Sousa Silva, Marta ; Ponces Freire, Ana ; Ferreira, António E. N; Boccaletti, Stefano (Editor)

PLoS ONE, 2012, Vol.7(3), p.e32749 [Tạp chí có phản biện]

E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0032749

Toàn văn sẵn có

Trích dẫn Trích dẫn bởi
  • Nhan đề:
    Optimization of Time-Course Experiments for Kinetic Model Discrimination (Kinetic Model Discrimination)
  • Tác giả: Lages, Nuno F ; Cordeiro, Carlos ; Sousa Silva, Marta ; Ponces Freire, Ana ; Ferreira, António E. N
  • Boccaletti, Stefano (Editor)
  • Chủ đề: Research Article ; Biology ; Computer Science ; Mathematics ; Genetics And Genomics ; Computational Biology ; Computer Science ; Biochemistry ; Mathematics
  • Là 1 phần của: PLoS ONE, 2012, Vol.7(3), p.e32749
  • Mô tả: Systems biology relies heavily on the construction of quantitative models of biochemical networks. These models must have predictive power to help unveiling the underlying molecular mechanisms of cellular physiology, but it is also paramount that they are consistent with the data resulting from key experiments. Often, it is possible to find several models that describe the data equally well, but provide significantly different quantitative predictions regarding particular variables of the network. In those cases, one is faced with a problem of model discrimination, the procedure of rejecting inappropriate models from a set of candidates in order to elect one as the best model to use for prediction. ; In this work, a method is proposed to optimize the design of enzyme kinetic assays with the goal of selecting a model among a set of candidates. We focus on models with systems of ordinary differential equations as the underlying mathematical description. The method provides a design where an extension of the Kullback-Leibler distance, computed over the time courses predicted by the models, is maximized. Given the asymmetric nature this measure, a generalized differential evolution algorithm for multi-objective optimization problems was used. ; The kinetics of yeast glyoxalase I (EC 4.4.1.5) was chosen as a difficult test case to evaluate the method. Although a single-substrate kinetic model is usually considered, a two-substrate mechanism has also been proposed for this enzyme. We designed an experiment capable of discriminating between the two models by optimizing the initial substrate concentrations of glyoxalase I, in the presence of the subsequent pathway enzyme, glyoxalase II (EC 3.1.2.6). This discriminatory experiment was conducted in the laboratory and the results indicate a two-substrate mechanism for the kinetics of yeast glyoxalase I.
  • Ngôn ngữ: English
  • Số nhận dạng: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0032749

Đang tìm Cơ sở dữ liệu bên ngoài...