Abstract
In the preceding chapters many aspects of metabolite quantification and relation to trait and disease phenotypes have been described, in particular the linkage of intermediate metabolic traits to genetic heterogeneities. Although many analyses start on the genome-wide level, they end up picking out single polymorphisms or other variations and study these in detail. This reductionist approach is very common in molecular biology and has proven hugely successful over the past decades. In recent years however, a second paradigm has become increasingly popular, namely that of integrating multiple such analyses into larger ones commonly called models. This paradigm, nowadays, is known as systems biology and is expected to penetrate many classical molecular analyses.
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References
Kitano H (2002) Systems biology: a brief overview. Science 295:1662–1664
Gille C, Bölling C, Hoppe A et al (2010) HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology. Mol Syst Biol 6:411
Orth JD, Conrad TM, Na J et al (2011) A comprehensive genome-scale reconstruction of Escherichia coli metabolism–2011. Mol Syst Biol 7:535
Thiele I, Palsson BØ (2010) A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc 5:93–121
Moriya Y, Itoh M, Okuda S, Yoshizawa AC, Kanehisa M (2007) KAAS: an automatic genome annotation and pathway reconstruction server. Nucleic Acids Res 35:W182–W185
Karp PD, Paley SM, Krummenacker M et al (2009) Pathway tools version 13.0: integrated software for pathway/genome informatics and systems biology. Brief Bioinform 11:40–79
Aziz RK, Bartels D, Best AA et al (2008) The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9:75
Durot M, Bourguignon PY, Schachter V (2009) Genome-scale models of bacterial metabolism: reconstruction and applications. FEMS Microbiol Rev 33:164–190
Gehlenborg N, O’Donoghue SI, Baliga NS et al (2010) Visualization of omics data for systems biology. Nat Methods 7:S56–S68
Kanehisa M, Goto S, Sato Y, Furumichi M, Tanabe M (2011) KEGG for integration and interpretation of large-scale molecular data sets. Nucleic Acids Res 40:D109–D114
Casp R, Altman T, Dale JM et al (2010) The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res 38:D473–D479
Overbeek R, Begley T, Butler RM et al (2005) The subsystems approach to genome annotation and its use in the project to annotate 1000 genomes. Nucleic Acids Res 33:5691–5702
Schellenberger J (2010) BiGG: a Biochemical Genetic and Genomic knowledgebase of large scale metabolic reconstructions. BMC Bioinformatics 11:213
Feist AM, Herrgård MJ, Thiele I, Reed JL, Palsson BØ (2009) Reconstruction of biochemical networks in microorganisms. Nat Rev Microbiol 7:129–143
Pitkänen E, Rousu J, Ukkonen E (2010) Computational methods for metabolic reconstruction. Curr Opin Biotechnol 21:70–77
Francke C, Siezen RJ, Teusink B (2005) Reconstructing the metabolic network of a bacterium from its genome. Trends Microbiol 13:550–558
Covert MW, Schilling CH, Famili I et al (2001) Metabolic modeling of microbial strains in silico. Trends Biochem Sci 2:179–186
Oberhardt MA, Palsson BØ, Papin JA (2009) Applications of genome-scale metabolic reconstructions. Mol Syst Biol 5:320
Karp PD, Caspi R (2011) A survey of metabolic databases emphasizing the MetaCyc family. Arch Toxicol 85:1015–1033
Delcher AL, Harmon D, Kasif S, White O, Salzberg SL (1999) Improved microbial gene identification with GLIMMER. Nucleic Acids Res 27:4636–4641
Borodovsky M, Lomsadze A (2011) Eukaryotic gene prediction using GeneMark.hmm-E and GeneMark-ES. Curr Protoc Bioinform Chapter 4:Unit 4.6.1–4.6.10
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410
Pearson WR (1990) Rapid and sensitive sequence comparison with FASTP and FASTA. Methods Enzymol 183:63–98
The Universal Protein Resource (UniProt) (2009) Consortium, UniProt. Nucleic Acids Res 37: D169–D174
Médigue C, Moszer I (2007) Annotation, comparison and databases for hundreds of bacterial genomes. Res Microbiol 158:724–736
Apweiler R, Altwood TK, Bairoch A et al (2000) InterPro–an integrated documentation resource for protein families, domains and functional sites. Bioinformatics 16:1145–1150
Claudel-Renard C, Chevalet C, Faraut T, Kahn D (2003) Enzyme-specific profiles for genome annotation: PRIAM. Nucleic Acids Res 31:6633–6639
Seffernick JL, de Souza ML, Sadowsky MJ, Wackett LP (2001) Melamine deaminase and atrazine chlorohydrolase: 98 percent identical but functionally different. J Bacteriol 183:2405–2410
Palmer DR, Garrett JB, Sharma V et al (1999) Unexpected divergence of enzyme function and sequence: “N-acylamino acid racemase” is o-succinylbenzoate synthase. Biochemistry 38:4252–4258
Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Sayers EW (2011) GenBank. Nucleic Acids Res 39:D32–D37
Markowitz VM, Chen I-MA, Palaniappan K et al (2010) The integrated microbial genomes system: an expanding comparative analysis resource. Nucleic Acids Res 38:D382–D390
Pinney JW, Shirley MW, McConkey GA, Westhead DR (2005) metaSHARK: software for automated metabolic network prediction from DNA sequence and its application to the genomes of Plasmodium falciparum and Eimeria tenella. Nucleic Acids Res 33:1399–1409
Sun J, Zeng A-P (2004) IdentiCS–identification of coding sequence and in silico reconstruction of the metabolic network directly from unannotated low-coverage bacterial genome sequence. BMC Bioinformatics 5:112
Bairoch A (2000) The ENZYME database in 2000. Nucleic Acids Res 28:304–305
Scheer M, Grote A, Chang A et al (2011) BRENDA, the enzyme information system in 2011. Nucleic Acids Res 39:D670–D676
Ren Q, Chen K, Paulsen IT (2007) TransportDB: a comprehensive database resource for cytoplasmic membrane transport systems and outer membrane channels. Nucleic Acids Res 35:D274–D279
Fleischmann A, Darsiw M, Degtyarenko K et al (2004) IntEnz, the integrated relational enzyme database. Nucleic Acids Res 32:D434–D437
Mao X, Cai T, Olyarchuk JG, Wei L (2005) Automated genome annotation and pathway identification using the KEGG Orthology (KO) as a controlled vocabulary. Bioinformatics 21:3787–3793
Ma H, Zeng A-P (2003) Reconstruction of metabolic networks from genome data and analysis of their global structure for various organisms. Bioinformatics 19:270–277
Kümmel A, Panke S, Heinemann M (2006) Systematic assignment of thermodynamic constraints in metabolic network models. BMC Bioinformatics 7:512
Gardy JL, Liard MR, Chen F et al (2005) PSORTb v.2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis. Bioinformatics 21:617–623
Petersen TN, Brunak S, von Heijne G, Nielsen H (2011) SignalP 4.0: discriminating signal peptides from transmembrane regions. Nat Methods 8:785–786
Emanuelsson O, Brunak S, von Heijne G, Nielsen H (2007) Locating proteins in the cell using TargetP, SignalP and related tools. Nat Protoc 2:953–971
Liao L, Kim S, Tomb JF (2002) Genome comparisons based on profiles of metabolic pathways
Hong SH, Kim TY, Lee SY (2004) Phylogenetic analysis based on genome-scale metabolic pathway reaction content. Appl Microbiol Biotechnol 65:203–210
Kastenmüller G, Gasteiger J, Mewes HW (2008) An environmental perspective on large-scale genome clustering based on metabolic capabilities. Bioinformatics 24:i56–i62
Maltsev N, Glass E, Sulakhe D et al (2006) PUMA2–grid-based high-throughput analysis of genomes and metabolic pathways. Nucleic Acids Res 34:D369–D372
Haft DH, Selengut JD, Brinkac LM, Zafar N, White O (2005) Genome Properties: a system for the investigation of prokaryotic genetic content for microbiology, genome annotation and comparative genomics. Bioinformatics 21:293–306
Kastenmüller G, Schenk ME, Gasteiger J, Mewes HW (2009) Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes. Genome Biol 10:R28
Croes D, Couche F, Wodak SJ, van Helden J (2005) Metabolic pathFinding: inferring relevant pathways in biochemical networks. Nucleic Acids Res 33:W326–W330
Faust K, Croes D, van Helden J (2009) Metabolic pathfinding using RPAIR annotation. J Mol Biol 388:390–414
Blum T, Kohlbacher O (2008) MetaRoute: fast search for relevant metabolic routes for interactive network navigation and visualization. Bioinformatics 24:2108–2109
Arita M (2003) In silico atomic tracing by substrate-product relationships in Escherichia coli intermediary metabolism. Genome Res 13:2455–2466
Rahman SA, Advani P, Schunk R, Schrader R, Schomburg D (2005) Metabolic pathway analysis web service (Pathway Hunter Tool at CUBIC). Bioinformatics 21:1189–1193
Blum T, Kohlbacher O (2008) Using atom mapping rules for an improved detection of relevant routes in weighted metabolic networks. J Comput Biol 15:565–576
Pitkänen E, Jouhten P, Rousu J (2009) Inferring branching pathways in genome-scale metabolic networks. BMC Syst Biol 3:103
Orth JD, Palsson BØ (2010) Systematizing the generation of missing metabolic knowledge. Biotechnol Bioeng 107:403–412
Kumar VS, Dasika MS, Maranas CD (2007) Optimization based automated curation of metabolic reconstructions. BMC Bioinformatics 8:212
Schilling CH, Palsson BO (2000) Assessment of the metabolic capabilities of Haemophilus influenzae Rd through a genome-scale pathway analysis. J Theor Biol 203:249–283
Henry CS, DeJongh M, Best AA et al (2010) High-throughput generation, optimization and analysis of genome-scale metabolic models. Nat Biotechnol 28:977–982
Kumar VS, Maranas CD (2009) GrowMatch: an automated method for reconciling in silico/in vivo growth predictions. PLoS Comput Biol 5:e1000308
Breitling R, Vitkup D, Barrett MP (2008) New surveyor tools for charting microbial metabolic maps. Nat Rev Microbiol 6:156–161
Palsson BØ (2006) Systems biology: properties of reconstructed networks. Cambridge University Press, Cambridge
Papin JA, Price ND, Wiback SJ, Fell DA, Palsson BØ (2003) Metabolic pathways in the post-genome era. Trends Biochem Sci 28:250–258
Schuster S, Fell DA, Dandekar T (2000) A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks. Nat Biotechnol 18:326–332
Schilling CH, Letscher D, Palsson BØ (2000) Theory for the systemic definition of metabolic pathways and their use in interpreting metabolic function from a pathway-oriented perspective. J Theor Biol 203:229–248
Llaneras F, Picó J (2010) Which metabolic pathways generate and characterize the flux space? A comparison among elementary modes, extreme pathways and minimal generators. J Biomed Biotechnol 2010:753904
Price ND, Papin JA, Palsson BØ (2002) Determination of redundancy and systems properties of the metabolic network of Helicobacter pylori using genome-scale extreme pathway analysis. Genome Res 12:760–769
Segrè D, Vitkup D, Church GM (2002) Analysis of optimality in natural and perturbed metabolic networks. Proc Natl Acad Sci USA 99:15112–15117
Rojas I, Golebiewski M, Kania R et al (2007) Storing and annotating of kinetic data. In Silico Biol 7:S3–S44
Rizzi M, Baltes M, Theobald U, Reuss M (1997) In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: II. Mathematical model. Biotechnol Bioeng 55:592–608
Teusink B, Passarge J, Reijenga CA et al (2000) Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. Eur J Biochem 267:5313–5329
Blow N (2008) Metabolomics: biochemistry’s new look. Nature 455:697–700
Famili I, Mahadevan R, Palsson BØ (2005) k-Cone analysis: determining all candidate values for kinetic parameters on a network scale. Biophys J 88:1616–1625
Jamshidi N, Palsson BØ (2010) Mass action stoichiometric simulation models: incorporating kinetics and regulation into stoichiometric models. Biophys J 98:175–185
Jamshidi N, Palsson BØ (2008) Top-down analysis of temporal hierarchy in biochemical reaction networks. PLoS Comput Biol 4:e1000177
Price ND, Schellenberger J, Palsson BØ (2004) Uniform sampling of steady-state flux spaces: means to design experiments and to interpret enzymopathies. Biophys J 87:2172–2186
Schellenberger J, Palsson BØ (2009) Use of randomized sampling for analysis of metabolic networks. J Biol Chem 284:5457–5461
Bakker BM, van Eunen K, Jeneson JA et al (2010) Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models. Biochem Soc Trans 38:1294–1301
Arkin A, Shen P, Ross J (1997) A test case of correlation metric construction of a reaction pathway from measurements. Science 277:1275–1279
Vance W, Arkin A, Ross J (2002) Determination of causal connectivities of species in reaction networks. Proc Natl Acad Sci USA 99:5816–5821
Steuer R, Kurths J, Fiehn O, Weckwerth W (2003) Observing and interpreting correlations in metabolomic networks. Bioinformatics 19:1019–1026
Øksendal B (2005) Stochastic differential equations: an introduction with applications. Springer, New York
Camacho D, de la Fuente A, Mendes P (2005) The origin of correlations in metabolomics data. Metabolomics 1:53–63
Krumsiek J, Suhre K, Illig T, Adamski J, Theis FJ (2011) Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data. BMC Syst Biol 5:21
Schäfer J, Strimmer K, Jos’ FF et al (2005) Learning large-scale graphical Gaussian models from genomic data. AIP Conf Proc 776:263–276
Lee JM, Gianchandani EP, Eddy JA, Papin JA (2008) Dynamic analysis of integrated signaling, metabolic, and regulatory networks. PLoS Comput Biol 4:e1000086
de la Fuente A, Bing N, Hoeschele I, Mendes P (2004) Discovery of meaningful associations in genomic data using partial correlation coefficients. Bioinformatics 20:3565–3574
Magwene PM, Kim J (2004) Estimating genomic coexpression networks using first-order conditional independence. Genome Biol 5:R100
Wille A, Zimmerman P, Vranová E et al (2004) Sparse graphical Gaussian modeling of the isoprenoid gene network in Arabidopsis thaliana. Genome Biol 5:R92
Freudenberg J, Wang M, Yang Y, Li W (2009) Partial correlation analysis indicates causal relationships between GC-content, exon density and recombination rate in the human genome. BMC Bioinformatics 10(Suppl 1):S66
Keurentjes Joost JB, Fu J, Ric de Vos CH et al (2006) The genetics of plant metabolism. Nat Genet 38:842–849
Liebermeister W, Klipp E (2006) Bringing metabolic networks to life: integration of kinetic, metabolic, and proteomic data. Theor Biol Med Model 3:42
Berg JM, Tymoczko JL, Stryer L (2006) Biochemistry, 6th edn. W. H. Freeman, Cranbury
Holle R, Happich M, Löwel H, Wichmann HE, MONICA/KORA Study Group (2005) KORA–a research platform for population based health research. Gesundheitswesen 67(Suppl 1):S19–S25
Illig T, Gieger C, Zhai G et al (2010) A genome-wide perspective of genetic variation in human metabolism. Nat Genet 42:137–141
Newman MEJ, Girvan M (2004) Finding and evaluating community structure in networks. Phys Rev E 69:026113
Matsuzaka T, Shimano H, Yahagi N et al (2007) Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat Med 13:1193–1202
Eaton S, Bartlett K, Pourfarzam M (1996) Mammalian mitochondrial beta-oxidation. Biochem J 320:345–357
Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30
Duarte NC, Becker SA, Jamshidi N et al (2007) Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci USA 104:1777–1782
Ma H, Sorokin A, Mazein A et al (2007) The Edinburgh human metabolic network reconstruction and its functional analysis. Mol Syst Biol 3:135
Van Rijsbergen CJ (1979) Information retrieval, 2nd edn. Butterworth, London
Suhre K, Petersen AK, Mohney RP et al (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature 477:54–60
Altmaier E, Ramsay SL, Graber A et al (2008) Bioinformatics analysis of targeted metabolomics–uncovering old and new tales of diabetic mice under medication. Endocrinology 149:3478–3489
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Krumsiek, J., Stückler, F., Kastenmüller, G., Theis, F.J. (2012). Systems Biology Meets Metabolism. In: Suhre, K. (eds) Genetics Meets Metabolomics. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1689-0_17
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