Using a logical model to predict the growth of yeast

BackgroundA logical model of the known metabolic processes in S. cerevisiae was constructed from iFF708, an existing Flux Balance Analysis (FBA) model, and augmented with information from the KEGG online pathway database. The use of predicate logic as the knowledge representation for modelling enables an explicit representation of the structure of the metabolic network, and enables logical inference techniques to be used for model identification/improvement.ResultsCompared to the FBA model, the logical model has information on an additional 263 putative genes and 247 additional reactions. The correctness of this model was evaluated by comparison with iND750 (an updated FBA model closely related to iFF708) by evaluating the performance of both models on predicting empirical minimal medium growth data/essential gene listings.ConclusionROC analysis and other statistical studies revealed that use of the simpler logical form and larger coverage results in no significant degradation of performance compared to iND750.

[1]  Ney Lemke,et al.  Essentiality and damage in metabolic networks , 2004, Bioinform..

[2]  L. Hood,et al.  Reverse Engineering of Biological Complexity , 2007 .

[3]  Herschel Rabitz,et al.  Optimal identification of biochemical reaction networks. , 2004, Biophysical journal.

[4]  Kara Dolinski,et al.  Saccharomyces genome database: Underlying principles and organisation , 2004, Briefings Bioinform..

[5]  Bernhard O. Palsson,et al.  Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions , 2000, BMC Bioinformatics.

[6]  Christopher H. Bryant,et al.  Functional genomic hypothesis generation and experimentation by a robot scientist , 2004, Nature.

[7]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[8]  Ron D. Appel,et al.  ExPASy: the proteomics server for in-depth protein knowledge and analysis , 2003, Nucleic Acids Res..

[9]  Anthony G. Cohn,et al.  Qualitative Reasoning , 1987, Advanced Topics in Artificial Intelligence.

[10]  Luc De Raedt,et al.  Inductive Logic Programming: Theory and Methods , 1994, J. Log. Program..

[11]  Hiroyuki Ogata,et al.  KEGG: Kyoto Encyclopedia of Genes and Genomes , 1999, Nucleic Acids Res..

[12]  Carlos Gershenson,et al.  Classification of Random Boolean Networks , 2002, ArXiv.

[13]  Manuel C. Peitsch Membrane protein models , 1997 .

[14]  Stephen Muggleton,et al.  Combining Inductive Logic Programming, Active Learning and Robotics to Discover the Function of Genes , 2001, Electron. Trans. Artif. Intell..

[15]  E. Ruppin,et al.  Regulatory on/off minimization of metabolic flux changes after genetic perturbations. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Dmitrij Frishman,et al.  MIPS: analysis and annotation of genome information in 2007 , 2007, Nucleic Acids Res..

[17]  M. Kanehisa A database for post-genome analysis. , 1997, Trends in genetics : TIG.

[18]  B. Palsson,et al.  Large-scale evaluation of in silico gene deletions in Saccharomyces cerevisiae. , 2003, Omics : a journal of integrative biology.

[19]  Peter D. Karp,et al.  Eco Cyc: encyclopedia of Escherichia coli genes and metabolism , 1999, Nucleic Acids Res..

[20]  Peter A. Flach The Geometry of ROC Space: Understanding Machine Learning Metrics through ROC Isometrics , 2003, ICML.

[21]  S. Schuster,et al.  Metabolic network structure determines key aspects of functionality and regulation , 2002, Nature.

[22]  Kenneth J. Kauffman,et al.  Advances in flux balance analysis. , 2003, Current opinion in biotechnology.

[23]  Monica L. Mo,et al.  Global reconstruction of the human metabolic network based on genomic and bibliomic data , 2007, Proceedings of the National Academy of Sciences.

[24]  Markus J. Herrgård,et al.  Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model. , 2004, Genome research.

[25]  Stephen Muggleton,et al.  Developing a Logical Model of Yeast Metabolism , 2001, Electron. Trans. Artif. Intell..

[26]  P Mendes,et al.  Biochemistry by numbers: simulation of biochemical pathways with Gepasi 3. , 1997, Trends in biochemical sciences.

[27]  Ross D. King,et al.  On the use of qualitative reasoning to simulate and identify metabolic pathway , 2005, Bioinform..

[28]  Ivan Bratko,et al.  Prolog Programming for Artificial Intelligence , 1986 .

[29]  F. Doyle,et al.  Dynamic flux balance analysis of diauxic growth in Escherichia coli. , 2002, Biophysical journal.

[30]  Masaru Tomita,et al.  E-CELL: software environment for whole-cell simulation , 1999, Bioinform..

[31]  Carsten Peterson,et al.  Random Boolean network models and the yeast transcriptional network , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[32]  G. Church,et al.  Analysis of optimality in natural and perturbed metabolic networks , 2002 .

[33]  L. Hood,et al.  A Genomic Regulatory Network for Development , 2002, Science.

[34]  Ney Lemke,et al.  A Method to Identify Essential Enzymes in the Metabolism: Application to Escherichia Coli , 2003, CMSB.

[35]  Ronald W. Davis,et al.  Functional profiling of the Saccharomyces cerevisiae genome , 2002, Nature.

[36]  François Fages,et al.  Modelling and querying interaction networks in the biochemical abstract machine BIOCHAM , 2002 .

[37]  Robert G. Sargent,et al.  Validation and verification of simulation models , 1999, Proceedings of the 2004 Winter Simulation Conference, 2004..

[38]  B. Palsson,et al.  Genome-scale reconstruction of the Saccharomyces cerevisiae metabolic network. , 2003, Genome research.

[39]  Lisa Chong,et al.  Whole-istic Biology , 2002, Science.

[40]  Douglas B. Kell,et al.  Non-linear optimization of biochemical pathways: applications to metabolic engineering and parameter estimation , 1998, Bioinform..