Network-based prediction of human tissue-specific metabolism
Abstract
Direct in vivo investigation of mammalian metabolism is complicated by the distinct metabolic functions of different tissues. We present a computational method that successfully describes the tissue specificity of human metabolism on a large scale. By integrating tissue-specific gene- and protein-expression data with an existing comprehensive reconstruction of the global human metabolic network, we predict tissue-specific metabolic activity in ten human tissues. This reveals a central role for post-transcriptional regulation in shaping tissue-specific metabolic activity profiles. The predicted tissue specificity of genes responsible for metabolic diseases and tissue-specific differences in metabolite exchange with biofluids extend markedly beyond tissue-specific differences manifest in enzyme-expression data, and are validated by large-scale mining of tissue-specificity data. Our results establish a computational basis for the genome-wide study of normal and abnormal human metabolism in a tissue-specific manner.
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Network-based approaches are likely to provide the best hope of integrating all this information by allowing a complete overview of the rumen microbiome because they can capture fundamental properties including taxonomy, functional similarity, metabolic processes, co-expression, and gene-sharing.
“Network-based approaches are likely to provide the best hope of integrating all this information by allowing a complete overview of the rumen microbiome as they are capable of capturing the fundamental properties of the microbial ecosystem including taxonomy (Barberan et al., 2012), functional similarity (Martiny et al., 2015), metabolic processes (Shlomi et al., 2008), co-expression (Zhang and”
From Addressing global ruminant agricultural challenges through understanding the rumen microbiome: past, present, and future (2018) · cites this paper as Shlomi et al., 2008
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
KEGG: Kyoto Encyclopedia of Genes and Genomes
Kanehisa, M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.27 · Cited by 37,077 · see citing works
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232 · see citing works
A gene atlas of the mouse and human protein-encoding transcriptomes
Su, A. I., Wiltshire, T., Batalov, S., Lapp, H., Ching, K. A., Block, D., Zhang, J., Soden, R., Hayakawa, M., Kreiman, G., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400782101 · Cited by 3,475 · see citing works
HMDB: the Human Metabolome Database
Wishart, D. S., Tzur, D., Knox, C., Eisner, R., Guo, A. C., Young, N., Cheng, D., Jewell, K., Arndt, D., Sawhney, S., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkl923 · Cited by 3,219 · see citing works
Integration of biological networks and gene expression data using Cytoscape
Cline, M. S., Smoot, M., Cerami, E., Kuchinsky, A., Landys, N., Workman, C., Christmas, R., Avila-Campilo, I., Creech, M., Gross, B., et al. (2007) · Nature Protocols · doi:10.1038/nprot.2007.324 · Cited by 2,507 · see citing works
Global reconstruction of the human metabolic network based on genomic and bibliomic data
Duarte, N. C., Becker, S. A., Jamshidi, N., Thiele, I., Mo, M. L., Vo, T. D., Srivas, R., & Palsson, B. Ø. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610772104 · Cited by 1,374 · see citing works
Self-citationYanai, I., Benjamin, H., Shmoish, M., Chalifa-Caspi, V., Shklar, M., Ophir, R., Bar-Even, A., Horn-Saban, S., Safran, M., Domany, E., et al. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti042 · Cited by 1,300 · see citing works
Burgard, A. P., Pharkya, P., & Maranas, C. D. (2003) · Biotechnology and Bioengineering · doi:10.1002/bit.10803 · Cited by 1,262 · see citing works
Understanding the control of metabolism
(1997) · Choice Reviews Online · doi:10.5860/choice.34-6252 · Cited by 1,230 · see citing works
The effects of alternate optimal solutions in constraint-based genome-scale metabolic models
Mahadevan, R., & Schilling, C. H. (2003) · Metabolic Engineering · doi:10.1016/j.ymben.2003.09.002 · Cited by 1,203 · see citing works
Andersen, J., Lam, Y. W., Leung, A. K. L., Ong, S., Lyon, C. E., Lamond, A. I., & Mann, M. (2005) · Nature · doi:10.1038/nature03207 · Cited by 1,152 · see citing works
Genome-scale models of microbial cells: evaluating the consequences of constraints
Price, N. D., Reed, J. L., & Palsson, B. Ø. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro1023 · Cited by 1,024 · see citing works
Self-citationBRENDA, the enzyme database: updates and major new developments
Schomburg, I. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh081 · Cited by 952 · see citing works
Saier, M. H. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj001 · Cited by 848 · see citing works
Integrating high-throughput and computational data elucidates bacterial networks
Covert, M. W., Knight, E. M., Reed, J. L., Herrgard, M. J., & Palsson, B. O. (2004) · Nature · doi:10.1038/nature02456 · Cited by 792 · see citing works
Self-citationMendelian Inheritance in Man and Its Online Version, OMIM
McKusick, V. A. (2007) · The American Journal of Human Genetics · doi:10.1086/514346 · Cited by 731 · see citing works
Systematic evaluation of objective functions for predicting intracellular fluxes in Escherichia coli
Schuetz, R. J., Kuepfer, L., & Sauer, U. (2007) · Molecular Systems Biology · doi:10.1038/msb4100162 · Cited by 684 · see citing works
Hubbard, T., Aken, B. L., Beal, K. M., Ballester, B., Cáccamo, M., Chen, Y., Clarke, L., Coates, G. M. P., Cunningham, F. M., Cutts, T., et al. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl996 · Cited by 637 · see citing works
Human protein reference database--2006 update
Mishra, G. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj141 · Cited by 601 · see citing works
A developmental view of microRNA function
Zhao, Y., & SRIVASTAVA, D. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.02.006 · Cited by 582 · see citing works
Branched-Chain Amino Acids: Enzyme and Substrate Regulation
Brosnan, J. T., & Brosnan, M. E. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.1.207s · Cited by 577 · see citing works
RAR and RXR modulation in cancer and metabolic disease
Altucci, L., Leibowitz, M. D., Ogilvie, K. M., de Lera, A. R., & Gronemeyer, H. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2397 · Cited by 517 · see citing works
Computational prediction of human metabolic pathways from the complete human genome
Romero, P. R., Wagg, J., GREEN, M. L., Kaiser, D., Krummenacker, M., & Karp, P. D. (2004) · Genome biology · doi:10.1186/gb-2004-6-1-r2 · Cited by 512 · see citing works
Regulatory on/off minimization of metabolic flux changes after genetic perturbations
Shlomi, T., Berkman, O., & Ruppin, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406346102 · Cited by 458 · see citing works
Self-citationThe Edinburgh human metabolic network reconstruction and its functional analysis
Ma, H., Sorokin, A., Mazein, A., Selkov, A., Selkov, E., Demin, O., & Goryanin, I. (2007) · Molecular Systems Biology · doi:10.1038/msb4100177 · Cited by 435 · see citing works
Genome-scale microbial in silico models: the constraints-based approach
Price, N. D., Papin, J. A., Schilling, C. H., & Palsson, B. Ø. (2003) · Trends in biotechnology · doi:10.1016/s0167-7799(03)00030-1 · Cited by 401 · see citing works
Self-citationFamili, I., Förster, J., Nielsen, J., & Palsson, B. O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2235812100 · Cited by 353 · see citing works
Self-citationObesity-related derangements in metabolic regulation
Muoio, D. M., & Newgard, C. B. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142512 · Cited by 345 · see citing works
Lipid metabolic enzymes: emerging drug targets for the treatment of obesity
Shi, Y., & Burn, P. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1469 · Cited by 333 · see citing works
Fong, S. S., & Palsson, B. Ø. (2004) · Nature Genetics · doi:10.1038/ng1432 · Cited by 297 · see citing works
Self-citationErmineJ: Tool for functional analysis of gene expression data sets
Lee, H. K., Braynen, W., Keshav, K. D., & Pavlidis, P. (2005) · BMC Bioinformatics · doi:10.1186/1471-2105-6-269 · Cited by 278 · see citing works
Daran-Lapujade, P. A. S., Jansen, M. L. A., Daran, J.-M. G., van Gulik, W. M., de Winde, J. H., & Pronk, J. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309578200 · Cited by 274 · see citing works
Shlomi, T., Eisenberg, Y., Sharan, R., & Ruppin, E. (2007) · Molecular Systems Biology · doi:10.1038/msb4100141 · Cited by 254 · see citing works
Self-citationDaran-Lapujade, P. A. S., Rossell, S., van Gulik, W. M., Luttik, M. A. H., de Groot, M. J. L., Slijper, M., Heck, A. J. R., Daran, J.-M. G., de Winde, J. H., Westerhoff, H. V., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707476104 · Cited by 248 · see citing works
Evidence for reduction of norepinephrine uptake sites in the failing human heart
Böhm, M., Rosée, K. L., Schwinger, R. H., & Erdmann, E. (1995) · Journal of the American College of Cardiology · doi:10.1016/0735-1097(94)00353-r · Cited by 235 · see citing works
A DNA microarray survey of gene expression in normal human tissues
Shyamsundar, R., Kim, Y. H., Higgins, J., Montgomery, K. D., Jorden, M. A., Sethuraman, A., van de Rijn, M., Botstein, D., Brown, P. O., & Pollack, J. R. (2005) · Genome biology · doi:10.1186/gb-2005-6-3-r22 · Cited by 226 · see citing works
Integration of gene expression data into genome-scale metabolic models
Åkesson, M., Förster, J., & Nielsen, J. (2004) · Metabolic Engineering · doi:10.1016/j.ymben.2003.12.002 · Cited by 203 · see citing works
GeneNote: whole genome expression profiles in normal human tissues
Shmueli, O., Horn‐Saban, S., Chalifa‐Caspi, V., et al. (2003) · Comptes Rendus Biologies · doi:10.1016/j.crvi.2003.09.012 · Cited by 173 · see citing works
Elevated Rates of Protein Secretion, Evolution, and Disease Among Tissue-Specific GenesPreprint
Winter, E. E., Goodstadt, L., & Ponting, C. P. (2004) · Genome Research · doi:10.1101/gr.1924004 · Cited by 172 · see citing works
Extreme Pathway Analysis of Human Red Blood Cell Metabolism
Wiback, S. J., & Palsson, B. Ø. (2002) · Biophysical Journal · doi:10.1016/s0006-3495(02)75210-7 · Cited by 167 · see citing works
Self-citationComputer model for glucose‐limited growth of a single cell of Escherichia coli B/r‐A
Domach, M. M., Leung, S. K., Cahn, R. E., et al. (1984) · Biotechnology and Bioengineering · doi:10.1002/bit.260260925 · Cited by 157 · see citing works
Vo, T. D., Greenberg, H. J., & Palsson, B. Ø. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403782200 · Cited by 154 · see citing works
Self-citationRossell, S., van der Weijden, C. C., Lindenbergh, A., van Tuijl, A., Francke, C., Bakker, B. M., & Westerhoff, H. V. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509831103 · Cited by 134 · see citing works
Database of mRNA gene expression profiles of multiple human organsPreprint
Son, C., Bilke, S., Davis, S. R., Greer, B. T., Wei, J. S., Whiteford, C. C., Chen, Q., Cenacchi, N., & Khan, J. I. (2005) · Genome Research · doi:10.1101/gr.3124505 · Cited by 130 · see citing works
Inborn errors of metabolism: the flux from Mendelian to complex diseases
Lanpher, B. C., Brunetti‐Pierri, N., & Lee, B. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1880 · Cited by 121 · see citing works
Levine, D., Haynor, D. R., Castle, J. C., Stepaniants, S. B., Pellegrini, M. A., Mao, M., & Johnson, J. M. (2006) · Genome biology · doi:10.1186/gb-2006-7-10-r93 · Cited by 109 · see citing works
Use of network analysis of metabolic systems in bioengineering
Schuster, S., Klamt, S., Weckwerth, W., et al. (2002) · Bioprocess and Biosystems Engineering · doi:10.1007/s004490100253 · Cited by 76 · see citing works
Fatal infantile neuromuscular presentation of glycogen storage disease type IV
Tay, S. K. H., Akman, H. O., Chung, W. K., et al. (2004) · Neuromuscular Disorders · doi:10.1016/j.nmd.2003.12.006 · Cited by 73 · see citing works
Greene, H. L., Brown, B. I., McClenathan, D. T., et al. (1988) · Hepatology · doi:10.1002/hep.1840080219 · Cited by 64 · see citing works
Yan, Q., & Sadée, W. (2000) · AAPS PharmSci · doi:10.1208/ps020320 · Cited by 50 · see citing works
Metabolomic biomarkers: search, discovery and validation
Kell, D. B. (2007) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.7.4.329 · Cited by 50 · see citing works
Bilu, Y., Shlomi, T., Barkai, N., & Ruppin, E. (2005) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0020106 · Cited by 36 · see citing works
Self-citationChatziioannou, A. A., Palaiologos, G., & Kolisis, F. N. (2003) · Metabolic Engineering · doi:10.1016/s1096-7176(03)00029-6 · Cited by 25 · see citing works
Lee, S. B., & Bailey, J. E. (2000) · Biotechnology and Bioengineering · doi:10.1002/(sici)1097-0290(20000320)67:6 · Cited by 6 · see citing works
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- Authors
- Shlomi, T., Cabili, M. N., Herrgård, M. J., Palsson, B. Ø., & Ruppin, E.
- Affiliations
- Tel Aviv University (IL)
- University of California San Diego (US)
- Corresponding author
- Shlomi, Tomer
- Ruppin, Eytan
- Venue
- Nature Biotechnology
- Published
- 2008-08-17
- Volume
- 26
- Issue
- 9
- Pages
- 1003-1010
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2154061034
- Cited by
- 637
- References
- 55
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 21 · 2023: 18 · 2022: 23 · 2021: 22 · 2020: 27 · 2019: 66 · 2018: 36 · 2017: 46 · 2016: 38 · 2015: 40 · 2014: 59 · 2013: 48 · 2012: 56
- FWCI
- 15.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research
- Israel Science Foundation
- Tel Aviv University
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM071808, GM071808)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- tissue-specific metabolism, human metabolic network, genome-scale metabolic models, constraint-based metabolic modeling, gene expression data, protein expression data, post-transcriptional regulation, metabolic disorders
- MeSH terms
- Cell Physiological Phenomena, Gene Expression Regulation, Humans, Models, Genetic, Software, Reproducibility of Results, Models, Statistical, Genome, Human, Computational Biology, Gene Expression Profiling, Databases, Protein, Metabolic Networks and Pathways
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