A comprehensive gene regulatory network for the diauxic shift in Saccharomyces cerevisiae

Existing machine-readable resources for large-scale gene regulatory networks usually do not provide context information characterizing the activating conditions for a regulation and how targeted genes are affected. Although this information is essentially required for data interpretation, available networks are often restricted to not condition-dependent, non-quantitative, plain binary interactions as derived from high-throughput screens. In this article, we present a comprehensive Petri net based regulatory network that controls the diauxic shift in Saccharomyces cerevisiae. For 100 specific enzymatic genes, we collected regulations from public databases as well as identified and manually curated >400 relevant scientific articles. The resulting network consists of >300 multi-input regulatory interactions providing (i) activating conditions for the regulators; (ii) semi-quantitative effects on their targets; and (iii) classification of the experimental evidence. The diauxic shift network compiles widespread distributed regulatory information and is available in an easy-to-use machine-readable form. Additionally, we developed a browsable system organizing the network into pathway maps, which allows to inspect and trace the evidence for each annotated regulation in the model.

[1]  Julio Collado-Vides,et al.  RegulonDB version 7.0: transcriptional regulation of Escherichia coli K-12 integrated within genetic sensory response units (Gensor Units) , 2010, Nucleic Acids Res..

[2]  Sunwon Park,et al.  Colored Petri net modeling and simulation of signal transduction pathways. , 2006, Metabolic engineering.

[3]  Tadao Murata,et al.  Petri nets: Properties, analysis and applications , 1989, Proc. IEEE.

[4]  Charles Boone,et al.  Identifying transcription factor functions and targets by phenotypic activation , 2006, Proceedings of the National Academy of Sciences.

[5]  Sunwon Park,et al.  Knowledge representation model for systems-level analysis of signal transduction networks. , 2004, Genome informatics. International Conference on Genome Informatics.

[6]  A. Kastaniotis,et al.  The biochemistry of peroxisomal β-oxidation in the yeast Saccharomyces cerevisiae , 2003 .

[7]  D. Botstein,et al.  Genomic expression programs in the response of yeast cells to environmental changes. , 2000, Molecular biology of the cell.

[8]  Steven M. Gallo,et al.  REDfly v3.0: toward a comprehensive database of transcriptional regulatory elements in Drosophila , 2010, Nucleic Acids Res..

[9]  W. Hsu,et al.  Handbook of Research on Computational Methodologies in Gene Regulatory Networks , 2009 .

[10]  Nicola J. Mulder,et al.  From sets to graphs: towards a realistic enrichment analysis of transcriptomic systems , 2011, Bioinform..

[11]  G. Hong,et al.  Nucleic Acids Research , 2015, Nucleic Acids Research.

[12]  D. Galas,et al.  DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. , 1978, Nucleic acids research.

[13]  Hiroaki Kitano,et al.  CellDesigner: a process diagram editor for gene-regulatory and biochemical networks , 2003 .

[14]  M. M. Garner,et al.  A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system , 1981, Nucleic Acids Res..

[15]  Jeffrey H. Miller Experiments in molecular genetics , 1972 .

[16]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[17]  Patrick J. Killion,et al.  Genetic reconstruction of a functional transcriptional regulatory network , 2007, Nature Genetics.

[18]  F. Robert,et al.  Transcriptional regulation of nonfermentable carbon utilization in budding yeast. , 2010, FEMS yeast research.

[19]  Edgar Wingender,et al.  The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation , 2008, Briefings Bioinform..

[20]  D. Kemp,et al.  Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Lieb,et al.  ChIP-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments. , 2004, Genomics.

[22]  James R Broach,et al.  How Saccharomyces responds to nutrients. , 2008, Annual review of genetics.

[23]  Tae-Min Kim,et al.  Advances in analysis of transcriptional regulatory networks , 2011, Wiley interdisciplinary reviews. Systems biology and medicine.

[24]  Nicola J. Rinaldi,et al.  Transcriptional Regulatory Networks in Saccharomyces cerevisiae , 2002, Science.

[25]  Ina Koch,et al.  Petri Nets and GRN Models , 2010 .

[26]  H. D. Vanguilder,et al.  Twenty-five years of quantitative PCR for gene expression analysis. , 2008, BioTechniques.

[27]  P. Collas The Current State of Chromatin Immunoprecipitation , 2010, Molecular biotechnology.

[28]  L. Aravind,et al.  Comprehensive analysis of combinatorial regulation using the transcriptional regulatory network of yeast. , 2006, Journal of molecular biology.

[29]  E. Wingender,et al.  A compilation of composite regulatory elements affecting gene transcription in vertebrates. , 1995, Nucleic acids research.

[30]  Hiroaki Kitano,et al.  The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models , 2003, Bioinform..

[31]  Hans-Joachim Schüller,et al.  Transcriptional control of nonfermentative metabolism in the yeast Saccharomyces cerevisiae , 2003, Current Genetics.

[32]  David J. Arenillas,et al.  JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles , 2009, Nucleic Acids Res..

[33]  R. Küffner,et al.  Petri Nets with Fuzzy Logic (PNFL): Reverse Engineering and Parametrization , 2010, PloS one.

[34]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.

[35]  A. Kastaniotis,et al.  The biochemistry of peroxisomal beta-oxidation in the yeast Saccharomyces cerevisiae. , 2003, FEMS microbiology reviews.

[36]  Marek S Skrzypek,et al.  Using the Saccharomyces Genome Database (SGD) for analysis of genomic information. , 2011, Current protocols in bioinformatics.

[37]  Alexandre P. Francisco,et al.  YEASTRACT: providing a programmatic access to curated transcriptional regulatory associations in Saccharomyces cerevisiae through a web services interface , 2010, Nucleic Acids Res..

[38]  Wolfgang Reisig,et al.  Modeling in Systems Biology, The Petri Net Approach , 2010, Computational Biology.

[39]  Markus J. Herrgård,et al.  Integrated analysis of regulatory and metabolic networks reveals novel regulatory mechanisms in Saccharomyces cerevisiae. , 2006, Genome research.

[40]  Albertha J. M. Walhout,et al.  Unraveling transcription regulatory networks by protein-DNA and protein-protein interaction mapping. , 2006, Genome research.

[41]  Hanspeter Rottensteiner,et al.  The biochemistry of oleate induction: transcriptional upregulation and peroxisome proliferation. , 2006, Biochimica et biophysica acta.