Hierarchical Organization of Modularity in Metabolic Networks
Open accessAbstract
Spatially or chemically isolated functional modules composed of several cellular components and carrying discrete functions are considered fundamental building blocks of cellular organization, but their presence in highly integrated biochemical networks lacks quantitative support. Here, we show that the metabolic networks of 43 distinct organisms are organized into many small, highly connected topologic modules that combine in a hierarchical manner into larger, less cohesive units, with their number and degree of clustering following a power law. Within Escherichia coli , the uncovered hierarchical modularity closely overlaps with known metabolic functions. The identified network architecture may be generic to system-level cellular organization.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Such networks were first constructed based on metabolic pathways, with metabolites as nodes and enzymatic conversions as edges.
“Such networks were first constructed based on metabolic pathways, with the metabolites corresponding to the nodes and the enzymatic conversions to the edges [65, 66].”
From Multi-omics approaches to disease (2017) · cites this paper as [66]
Previous work using complex networks theory has quantitatively tackled the problem of hierarchy.
“Although previous work using complex networks theory has quantitatively tackled the problem [3, 4, 22-25, 27-31], some questions remain:”
From On the origins of hierarchy in complex networks (2013) · cites this paper as [24]
Developing a multiscale representation requires analyzing communities in biological networks at more than one scale, defining and identifying communities at each scale, and tracing containment to infer a hierarchical map.
“Developing a multiscale representation requires analyzing communities in biological networks at more than one scale. Communities (clusters of highly interconnected nodes) are first defined and identified at each of multiple scales; subsequently, communities that are contained within other communities, in whole or in part, can be traced to infer a hierarchical map (Figure 2) (Dotan-Cohen et al., 20”
From Mapping the multiscale structure of biological systems (2021) · cites this paper as Ravasz et al., 2002
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Collective dynamics of ‘small-world’ networks
Watts, D. J., & Strogatz, S. H. (1998) · Nature · doi:10.1038/30918 · Cited by 43,060 · see citing works
Emergence of Scaling in Random Networks
Barabási, A.-L., & Albert, R. (1999) · Science · doi:10.1126/science.286.5439.509 · Cited by 36,135 · see citing works
Statistical mechanics of complex networks
Albert, R., & Barabási, A.-L. (2002) · Reviews of Modern Physics · doi:10.1103/revmodphys.74.47 · Cited by 20,471 · see citing works
Community structure in social and biological networks
Girvan, M., & Newman, M. E. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122653799 · Cited by 15,502 · see citing works
Cluster analysis and display of genome-wide expression patterns
Eisen, M. B., Spellman, P. T., Brown, P. O., & Botstein, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14863 · Cited by 12,617 · see citing works
The Large-Scale Organization of Metabolic Networks
Jeong, H., Tombor, B., Albert, R., Oltvai, Z. N., & Barabási, A.-L. (2000) · Nature · doi:10.1038/35036627 · Cited by 4,972 · see citing works
Self-citationSystems biology: a brief overview
Kitano, H. (2002) · Science · doi:10.1126/science.1069492 · Cited by 4,265 · see citing works
From molecular to modular cell biology.
Hartwell, L. H., Hopfield, J. J., Leibler, S., & Murray, A. W. (1999) · Nature · doi:10.1038/35011540 · Cited by 3,632 · see citing works
Network motifs in the transcriptional regulation network of Escherichia coli
Shen-Orr, S. S., Milo, R., Mangan, S., & Alon, U. S. (2002) · Nature Genetics · doi:10.1038/ng881 · Cited by 2,970 · see citing works
Robustness in bacterial chemotaxis
Alon, U. S., Surette, M. G., Barkai, N., & Leibler, S. (1999) · Nature · doi:10.1038/16483 · Cited by 1,129 · see citing works
Self-organization and identification of Web communities
Flake, G. W., Lawrence, S., Giles, C. L., & Coetzee, F. M. (2002) · Computer · doi:10.1109/2.989932 · Cited by 1,021 · see citing works
The small world inside large metabolic networks
Wagner, A., & Fell, D. A. (2001) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2001.1711 · Cited by 986 · see citing works
Schuster, S., Fell, D. A., & Dandekar, T. (2000) · Nature Biotechnology · doi:10.1038/73786 · Cited by 947 · see citing works
Large-scale topological and dynamical properties of the Internet
Vázquez, A., Pastor-Satorras, R., & Vespignani, A. (2002) · Physical Review E · doi:10.1103/physreve.65.066130 · Cited by 712 · see citing works
Schilling, C. H., Letscher, D., & Palsson, B. Ø. (2000) · Journal of Theoretical Biology · doi:10.1006/jtbi.2000.1073 · Cited by 664 · see citing works
Computational studies of gene regulatory networks: in numero molecular biology
Hasty, J., McMillen, D. R., Isaacs, F. J., & Collins, J. J. (2001) · Nature Reviews Genetics · doi:10.1038/35066056 · Cited by 588 · see citing works
Dorogovtsev, S. N., Goltsev, A. V., & Mendes, J. F. F. (2002) · Physical Review E · doi:10.1103/physreve.65.066122 · Cited by 540 · see citing works
Deterministic scale-free networks
Barabási, A.-Ĺ., Regan, E. R., & Vicsek, T. (2001) · Physica A Statistical Mechanics and its Applications · doi:10.1016/s0378-4371(01)00369-7 · Cited by 468 · see citing works
Karp, P. D. (2002) · Nucleic Acids Research · doi:10.1093/nar/30.1.56 · Cited by 451 · see citing works
WIT: integrated system for high-throughput genome sequence analysis and metabolic reconstruction
Overbeek, R. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.123 · Cited by 395 · see citing works
A MODEL OF LARGE-SCALE PROTEOME EVOLUTION
Solé, R. V., Pastor‐Satorras, R., Smith, E., & Kepler, T. B. (2002) · Advances in Complex Systems · doi:10.1142/s021952590200047x · Cited by 330 · see citing works
Dynamic modeling of gene expression data
Holter, N. S., Maritan, A., Cieplak, M., Fedoroff, N. V., & Banavar, J. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.4.1693 · Cited by 300 · see citing works
Scale-Free Behavior in Protein Domain Networks
Wuchty, S. (2001) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a003957 · Cited by 262 · see citing works
Cell signaling pathways as control modules: Complexity for simplicity?
Lauffenburger, D. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5031 · Cited by 255 · see citing works
Wrestling with pleiotropy: Genomic and topological analysis of the yeast gene expression network
Featherstone, D. E., & Broadie, K. (2002) · BioEssays · doi:10.1002/bies.10054 · Cited by 179 · see citing works
Control Motifs for Intracellular Regulatory Networks
Rao, C. V., & Arkin, A. P. (2001) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.3.1.391 · Cited by 119 · see citing works
Scale‐free networks in biology: new insights into the fundamentals of evolution?*
Wolf, Y. I., Karev, G. P., & Koonin, E. V. (2002) · BioEssays · doi:10.1002/bies.10059 · Cited by 112 · see citing works
Lorenz, A., & Whitby, M. C. (2014) · Figshare · doi:10.6084/m9.figshare.1197171.v4 · Cited by 22 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- [6]6. N. S. Holter, A. Maritan, M. Cieplak, N. V. Fedoroff, J. R. Banavar, Proc Natl Acad Sci Sci U S A 98, 1693 (2001).
- [23]23. D. E. Featherstone, K. Broadie, Bioessays 24 (3), 267 (2002).
- [26]26. M. Girvan, M. E. J. Newman, Proc. Natl. Acad. Sci. USA 99 , 7821 (2002).
- [29]29. R. P. Solé, D. E. Smith, R. Pastor-Satorras, T. Kepler, Santa Fe Preprint (available at http://www.santafe.edu/sfi/publications/wpabstract/200108041).
Cited by
Sorted by citations
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252 · see citing works
Fortunato, S. (2010) · Physics Reports · doi:10.1016/j.physrep.2009.11.002 · Cited by 11,293 · see citing works
Complex networks: structure and dynamics
BOCCALETTI, S., LATORA, V, MORENO, Y., CHAVEZ, M., & HWANG, D. (2006) · Physics Reports · doi:10.1016/j.physrep.2005.10.009 · Cited by 11,010 · see citing works
Network biology: understanding the cell's functional organization
Barabási, A.-L., & Oltvai, Z. N. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1272 · Cited by 7,903 · see citing works
Self-citationA General Framework for Weighted Gene Co-Expression Network Analysis
Zhang, B., & Horvath, S. (2005) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1128 · Cited by 5,684 · see citing works
The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans
The GTEx Consortium, Ardlie, K. G., Deluca, D. S., Segrè, A. V., Sullivan, T. J., Young, T. R., Gelfand, E. T., Trowbridge, C. A., Maller, J. B., Tukiainen, T., et al. (2015) · Science · doi:10.1126/science.1262110 · Cited by 5,062 · see citing works
Uncovering the overlapping community structure of complex networks in nature and society
Palla, G., Derényi, I., Farkas, I., & Vicsek, T. (2005) · Nature · doi:10.1038/nature03607 · Cited by 5,373 · see citing works
Network medicine: a network-based approach to human disease
Barabási, A.-L., Gulbahce, N., & Loscalzo, J. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2918 · Cited by 5,034 · see citing works
Self-citationFunctional cartography of complex metabolic networks
Guimerà, R., & Nunes Amaral, L. A. (2005) · Nature · doi:10.1038/nature03288 · Cited by 3,983 · see citing works
Multi-omics approaches to disease
Hasin, Y., Seldin, M., & Lusis, A. (2017) · Genome Biology · doi:10.1186/s13059-017-1215-1 · Cited by 2,953 · see citing works
Resolution limit in community detection
Fortunato, S., & Barthélemy, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605965104 · Cited by 3,024 · see citing works
Defining and identifying communities in networks
Radicchi, F., Castellano, C., Cecconi, F., Loreto, V., & Parisi, D. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400054101 · Cited by 2,450 · see citing works
Resting-state connectivity biomarkers define neurophysiological subtypes of depression
Drysdale, A. T., Grosenick, L., Downar, J., Dunlop, K., Mansouri, F., Meng, Y., Fetcho, R. N., Zebley, B., Oathes, D. J., Etkin, A., et al. (2017) · Nature Medicine · doi:10.1038/nm.4246 · Cited by 2,170 · see citing works
Hierarchical structure and the prediction of missing links in networks
Clauset, A., Moore, C., & Newman, M. E. J. (2008) · Nature · doi:10.1038/nature06830 · Cited by 2,171 · see citing works
Organization, development and function of complex brain networks
SPORNS, O., CHIALVO, D., KAISER, M., & HILGETAG, C. (2004) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2004.07.008 · Cited by 2,055 · see citing works
Interactome Networks and Human Disease
Vidal, M., Cusick, M. E., & Barabási, A.-L. (2011) · Cell · doi:10.1016/j.cell.2011.02.016 · Cited by 1,771 · see citing works
Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Zhang, B., Gaiteri, C., Bodea, L.-G., Wang, Z., McElwee, J., Podtelezhnikov, A. A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.030 · Cited by 1,657 · see citing works
Microbial co-occurrence relationships in the human microbiome
Faust, K., Sathirapongsasuti, J. F., Izard, J., Segata, N., Gevers, D., Raes, J., & Huttenhower, C. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002606 · Cited by 1,527 · see citing works
Highly nonrandom features of synaptic connectivity in local cortical circuits
Song, S., Sjöström, P. J., Reigl, M., Nelson, S., & Chklovskii, D. B. (2005) · PLoS Biology · doi:10.1371/journal.pbio.0030068 · Cited by 1,512 · see citing works
Genetics of gene expression and its effect on disease
Emilsson, V., Thorleifsson, G., Zhang, B., Leonardson, A. S., Zink, F., Zhu, J., Carlson, S., Helgason, A., Walters, G. B., Gunnarsdottir, S., et al. (2008) · Nature · doi:10.1038/nature06758 · Cited by 1,296 · see citing works
Transcriptional landscape of the prenatal human brain
Miller, J. A., Ding, S.-L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., Ebbert, A., Riley, Z. L., Royall, J. J., Aiona, K., et al. (2014) · Nature · doi:10.1038/nature13185 · Cited by 1,325 · see citing works
Gene expression elucidates functional impact of polygenic risk for schizophrenia
Fromer, M., Roussos, P., Sieberts, S. K., Johnson, J. S., Kavanagh, D. H., Perumal, T. M., Ruderfer, D. M., Oh, E. C., Topol, A., Shah, H. R., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4399 · Cited by 1,091 · see citing works
Random Walks on Complex Networks
Noh, J. D., & Rieger, H. (2004) · Physical Review Letters · doi:10.1103/physrevlett.92.118701 · Cited by 1,148 · see citing works
Inferring Genetic Networks and Identifying Compound Mode of Action via Expression Profiling
Gardner, T. S., di Bernardo, D., Lorenz, D., & Collins, J. J. (2003) · Science · doi:10.1126/science.1081900 · Cited by 1,117 · see citing works
Robustness of cellular functions
Stelling, J., Sauer, U., Szallasi, Z., Doyle, F. J., & Doyle, J. (2004) · Cell · doi:10.1016/j.cell.2004.09.008 · Cited by 1,049 · see citing works
Hyperbolic geometry of complex networks
Krioukov, D., Papadopoulos, F., Kitsak, M., Vahdat, A., & Boguñá, M. (2010) · Physical Review E · doi:10.1103/physreve.82.036106 · Cited by 1,059 · see citing works
Clustering in weighted networks
Opsahl, T., & Panzarasa, P. (2009) · Social Networks · doi:10.1016/j.socnet.2009.02.002 · Cited by 1,037 · see citing works
Eigengene networks for studying the relationships between co-expression modules
Langfelder, P., & Horvath, S. (2007) · BMC Systems Biology · doi:10.1186/1752-0509-1-54 · Cited by 867 · see citing works
Modularity from fluctuations in random graphs and complex networks
Guimerà, R., Sales-Pardo, M., & Amaral, L. A. N. (2004) · Physical Review E · doi:10.1103/physreve.70.025101 · Cited by 894 · see citing works
Variations in DNA elucidate molecular networks that cause disease
Chen, Y., Zhu, J., Lum, P. Y., Yang, X., Pinto, S., MacNeil, D. J., Zhang, C., Lamb, J., Edwards, S., Sieberts, S. K., et al. (2008) · Nature · doi:10.1038/nature06757 · Cited by 887 · see citing works
Morphological integration and developmental modularity
Klingenberg, C. P. (2008) · Annual Review of Ecology Evolution and Systematics · doi:10.1146/annurev.ecolsys.37.091305.110054 · Cited by 863 · see citing works
Development of large-scale functional brain networks in children
Supekar, K., Musen, M., & Menon, V. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000157 · Cited by 807 · see citing works
Functional organization of the transcriptome in human brain
Oldham, M. C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., & Geschwind, D. H. (2008) · Nature Neuroscience · doi:10.1038/nn.2207 · Cited by 752 · see citing works
Epigenomic Profiling Reveals DNA-Methylation Changes Associated with Major Psychosis
Mill, J., Tang, T., Kaminsky, Z., Khare, T., Yazdanpanah, S., Bouchard, L., Jia, P., Assadzadeh, A., Flanagan, J., Schumacher, A., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.01.008 · Cited by 773 · see citing works
Biological networks: the tinkerer as an engineer
Alon, U. (2003) · Science · doi:10.1126/science.1089072 · Cited by 706 · see citing works
Comparative Genomics of Centrality and Essentiality in Three Eukaryotic Protein-Interaction Networks
Hahn, M. W., & Kern, A. D. (2005) · Molecular Biology and Evolution · doi:10.1093/molbev/msi072 · Cited by 656 · see citing works
The Polygenic and Monogenic Basis of Blood Traits and Diseases
Vuckovic, D., Bao, E. L., Akbari, P., Lareau, C. A., Mousas, A., Jiang, T., Chen, M.-H., Raffield, L. M., Tardaguila, M., Huffman, J. E., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.008 · Cited by 671 · see citing works
Popularity versus similarity in growing networks
Papadopoulos, F., Kitsak, M., Serrano, M. Á., Boguñá, M., & Krioukov, D. (2012) · Nature · doi:10.1038/nature11459 · Cited by 634 · see citing works
Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression
Bai, B., Wang, X., Li, Y., Chen, P.-C., Yu, K., Dey, K. K., Yarbro, J. M., Han, X., Lutz, B. M., Rao, S., et al. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.015 · Cited by 632 · see citing works
“the two connected proteins) from proteins in the same cluster; (ii) calculating a topologically overlapping matrix (Ravasz et al., 2002) for the PPI network, and modularizing such a network into individual modules by the hybrid dynamic tree-cutting method (Langfelder and Horvath, 2008).”
BackgroundComputer‐Assisted Synthetic Planning: The End of the Beginning
Szymkuć, S., Gajewska, E. P., Klucznik, T., Molga, K., Dittwald, P., Startek, M., Bajczyk, M., & Grzybowski, B. A. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201506101 · Cited by 611 · see citing works
Conservation and evolution of gene coexpression networks in human and chimpanzee brains
Oldham, M. C., Horvath, S., & Geschwind, D. H. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605938103 · Cited by 566 · see citing works
Modular epistasis in yeast metabolism
Segrè, D., DeLuna, A., Church, G. M., & Kishony, R. (2005) · Nature Genetics · doi:10.1038/ng1489 · Cited by 575 · see citing works
Metabolomics and systems biology: making sense of the soup
KELL, D. (2004) · Current Opinion in Microbiology · doi:10.1016/j.mib.2004.04.012 · Cited by 529 · see citing works
Integrating Genetic and Network Analysis to Characterize Genes Related to Mouse Weight
Ghazalpour, A., Doss, S., Zhang, B., Wang, S., Plaisier, C., Castellanos, R., Brozell, A., Schadt, E. E., Drake, T. A., Lusis, A. J., et al. (2006) · PLoS Genetics · doi:10.1371/journal.pgen.0020130 · Cited by 462 · see citing works
Divergence of human and mouse brain transcriptome highlights Alzheimer disease pathways
Miller, J. A., Horvath, S., & Geschwind, D. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914257107 · Cited by 480 · see citing works
Comparison of co-expression measures: mutual information, correlation, and model based indices
Song, L., Langfelder, P., & Horvath, S. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-328 · Cited by 460 · see citing works
Understanding network concepts in modules
Dong, J., & Horvath, S. (2007) · BMC Systems Biology · doi:10.1186/1752-0509-1-24 · Cited by 455 · see citing works
A Systems Level Analysis of Transcriptional Changes in Alzheimer's Disease and Normal Aging
Miller, J. A., Oldham, M. C., & Geschwind, D. H. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4098-07.2008 · Cited by 385 · see citing works
Epstein–Barr virus and virus human protein interaction maps
Calderwood, M. A., Venkatesan, K., Xing, L., Chase, M. R., Vazquez, A., Holthaus, A. M., Ewence, A. E., Li, N., Hirozane-Kishikawa, T., Hill, D. E., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702332104 · Cited by 388 · see citing works
When is hub gene selection better than standard meta-analysis?
Langfelder, P., Mischel, P. S., & Horvath, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061505 · Cited by 313 · see citing works
Carter, S. L., Brechbühler, C. M., Griffin, M., & Bond, A. T. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth234 · Cited by 344 · see citing works
Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae
Reguly, T., Breitkreutz, A., Boucher, L., Breitkreutz, B.-J., Hon, G. C., Myers, C. L., Parsons, A., Friesen, H., Oughtred, R., Tong, A., et al. (2006) · Journal of Biology · doi:10.1186/jbiol36 · Cited by 326 · see citing works
Wang, M., Roussos, P., McKenzie, A., Zhou, X., Kajiwara, Y., Brennand, K. J., De Luca, G. C., Crary, J. F., Casaccia, P., Buxbaum, J. D., et al. (2016) · Genome Medicine · doi:10.1186/s13073-016-0355-3 · Cited by 314 · see citing works
Motifs, modules and games in bacteria
Wolf, D. M., & Arkin, A. P. (2003) · Current Opinion in Microbiology · doi:10.1016/s1369-5274(03)00033-x · Cited by 303 · see citing works
Network Organization of the Huntingtin Proteomic Interactome in Mammalian Brain
Shirasaki, D. I., Greiner, E. R., Al-Ramahi, I., Gray, M., Boontheung, P., Geschwind, D. H., Botas, J., Coppola, G., Horvath, S., Loo, J. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.05.024 · Cited by 297 · see citing works
Mason, M. J., Fan, G., Plath, K., Zhou, Q., & Horvath, S. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-327 · Cited by 243 · see citing works
DiffCoEx: a simple and sensitive method to find differentially coexpressed gene modules
Tesson, B. M., Breitling, R., & Jansen, R. C. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-497 · Cited by 244 · see citing works
Human Cancer Protein-Protein Interaction Network: A Structural Perspective
Kar, G., Gursoy, A., & Keskin, O. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000601 · Cited by 235 · see citing works
The Powerful Law of the Power Law and Other Myths in Network Biology
Lima-Mendez, G., & van Helden, J. (2009) · Molecular BioSystems · doi:10.1039/b908681a · Cited by 210 · see citing works
Green plants as intelligent organisms
Trewavas, A. (2005) · Trends in Plant Science · doi:10.1016/j.tplants.2005.07.005 · Cited by 212 · see citing works
A gene ontology inferred from molecular networks
Dutkowski, J., Kramer, M., Surma, M. A., Balakrishnan, R., Cherry, J. M., Krogan, N. J., & Ideker, T. (2013) · Nature Biotechnology · doi:10.1038/nbt.2463 · Cited by 184 · see citing works
Modeling formalisms in Systems Biology
Machado, D., Costa, R. S., Rocha, M., Ferreira, E. C., Tidor, B., & Rocha, I. (2011) · AMB Express · doi:10.1186/2191-0855-1-45 · Cited by 189 · see citing works
Bhardwaj, N., & Lu, H. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti398 · Cited by 186 · see citing works
Oldham, M. C., Langfelder, P., & Horvath, S. (2012) · BMC Systems Biology · doi:10.1186/1752-0509-6-63 · Cited by 154 · see citing works
Mathematical models in microbial systems biology
Stelling, J. (2004) · Current Opinion in Microbiology · doi:10.1016/j.mib.2004.08.004 · Cited by 164 · see citing works
On the origins of hierarchy in complex networks
Corominas-Murtra, B., Goñi, J., Solé, R. V., & Rodríguez-Caso, C. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300832110 · Cited by 160 · see citing works
A comprehensive modular map of molecular interactions in RB/E2F pathway
Calzone, L., Gelay, A., Zinovyev, A., Radvanyi, F., & Barillot, E. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.7 · Cited by 132 · see citing works
Sex Differences in the Expression of Drug-Metabolizing and Transporter Genes in Human Liver
Yang, L., & Li, Y. (2012) · Journal of Drug Metabolism & Toxicology · doi:10.4172/2157-7609.1000119 · Cited by 135 · see citing works
Hierarchical modularity of nested bow-ties in metabolic networks
Zhao, J., Yu, H., Luo, J.-H., Cao, Z.-W., & Li, Y.-X. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-386 · Cited by 128 · see citing works
The evolutionary origins of hierarchy
Mengistu, H., Huizinga, J., Mouret, J.-B., & Clune, J. (2016) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1004829 · Cited by 115 · see citing works
Modelling Crop Improvement in a G×E×M Framework via Gene–Trait–Phenotype Relationships
Messina, C., Hammer, G., Dong, Z., Podlich, D., & Cooper, M. (2009) · Crop Physiology · doi:10.1016/b978-0-12-374431-9.00010-4 · Cited by 121 · see citing works
The organization of the transcriptional network in specific neuronal classes
Winden, K. D., Oldham, M. C., Mirnics, K., Ebert, P. J., Swan, C. H., Levitt, P., Rubenstein, J. L., Horvath, S., & Geschwind, D. H. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.46 · Cited by 112 · see citing works
Romanoski, C. E., Che, N., Yin, F., Mai, N., Pouldar, D., Civelek, M., Pan, C., Lee, S., Vakili, L., Yang, W.-P., et al. (2011) · Circulation Research · doi:10.1161/circresaha.111.241869 · Cited by 115 · see citing works
Paparo, G. D., & Martin-Delgado, M. A. (2012) · Scientific Reports · doi:10.1038/srep00444 · Cited by 136 · see citing works
Gene-to-phenotype models and complex trait genetics
Cooper, M., Podlich, D. W., & Smith, O. S. (2005) · Australian Journal of Agricultural Research · doi:10.1071/ar05154 · Cited by 104 · see citing works
Spontaneous emergence of modularity in cellular networks
Solé, R. V., & Valverde, S. (2008) · Journal of The Royal Society Interface · doi:10.1098/rsif.2007.1108 · Cited by 102 · see citing works
Expression Quantitative Trait Loci Mapping With Multivariate Sparse Partial Least Squares Regression
Chun, H., & Keleş, S. (2009) · Genetics · doi:10.1534/genetics.109.100362 · Cited by 97 · see citing works
Emergent Complex Network Geometry
Wu, Z., Menichetti, G., Rahmede, C., & Bianconi, G. (2015) · Scientific Reports · doi:10.1038/srep10073 · Cited by 98 · see citing works
Network Medicine in Pathobiology
Lee, L. Y.-H., & Loscalzo, J. (2019) · The American Journal of Pathology · doi:10.1016/j.ajpath.2019.03.009 · Cited by 95 · see citing works
Xie, W., Wood, A. R., Lyssenko, V., Weedon, M. N., Knowles, J. W., Alkayyali, S., Assimes, T. L., Quertermous, T., Abbasi, F., Paananen, J., et al. (2013) · Diabetes · doi:10.2337/db12-0876 · Cited by 83 · see citing works
Post-GWAS: where next? More samples, more SNPs or more biology?
Marjoram, P., Zubair, A., & Nuzhdin, S. V. (2014) · Heredity · doi:10.1038/hdy.2013.52 · Cited by 74 · see citing works
VisANT 3.0: new modules for pathway visualization, editing, prediction and construction
Hu, Z., Ng, D. M., Yamada, T., Chen, C., Kawashima, S., Mellor, J., Linghu, B., Kanehisa, M., Stuart, J. M., & DeLisi, C. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm295 · Cited by 76 · see citing works
Mapping the multiscale structure of biological systems
Schaffer, L. V., & Ideker, T. (2021) · Cell Systems · doi:10.1016/j.cels.2021.05.012 · Cited by 75 · see citing works
Li, Z. (., Fang, X., & Sheng, O. R. L. (2018) · ACM Transactions on Management Information Systems · doi:10.1145/3131782 · Cited by 65 · see citing works
Complex quantum network geometries: Evolution and phase transitions
Bianconi, G., Rahmede, C., & Wu, Z. (2015) · Physical Review E · doi:10.1103/physreve.92.022815 · Cited by 63 · see citing works
Systems biology perspectives on minimal and simpler cells
Xavier, J. C., Patil, K. R., & Rocha, I. (2014) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00050-13 · Cited by 58 · see citing works
Network Analysis Identifies Mitochondrial Regulation of Epidermal Differentiation by MPZL3 and FDXR
Bhaduri, A., Ungewickell, A., Boxer, L. D., Lopez-Pajares, V., Zarnegar, B. J., & Khavari, P. A. (2015) · Developmental Cell · doi:10.1016/j.devcel.2015.10.023 · Cited by 60 · see citing works
Genetic architecture for human aggression: A study of gene–phenotype relationship in OMIM
Zhang‐James, Y., & Faraone, S. V. (2016) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32363 · Cited by 48 · see citing works
Correlation between structure and temperature in prokaryotic metabolic networks
Takemoto, K., Nacher, J. C., & Akutsu, T. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-303 · Cited by 40 · see citing works
Structural and dynamical analysis of biological networks
Klein, C., Marino, A., Sagot, M.-F., Vieira Milreu, P., & Brilli, M. (2012) · Briefings in Functional Genomics · doi:10.1093/bfgp/els030 · Cited by 34 · see citing works
Saba, V., Premi, E., Cristillo, V., Gazzina, S., Palluzzi, F., Zanetti, O., Gasparotti, R., Padovani, A., Borroni, B., & Grassi, M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00211 · Cited by 33 · see citing works
Blinov, M. L., Ruebenacker, O., & Moraru, I. I. (2008) · IET Systems Biology · doi:10.1049/iet-syb:20080092 · Cited by 25 · see citing works
Convergent Evolutionary Paths in Biological and Technological Networks
Solé, R. V., Valverde, S., & Rodriguez-Caso, C. (2011) · Evolution: Education and Outreach · doi:10.1007/s12052-011-0346-1 · Cited by 20 · see citing works
Measuring the hierarchy of feedforward networks
Corominas-Murtra, B., Rodríguez-Caso, C., Goñi, J., & Solé, R. (2011) · Chaos: An Interdisciplinary Journal of Nonlinear Science · doi:10.1063/1.3562548 · Cited by 16 · see citing works
Quantum Google algorithm: Construction and application to complex networks
Paparo, G. D., Müller, M., Comellas, F., & Martin-Delgado, M. A. (2014) · The European Physical Journal Plus · doi:10.1140/epjp/i2014-14150-y · Cited by 17 · see citing works
- Authors
- Ravasz, E., Somera, A. L., Mongru, D. A., Oltvai, Z. N., & Barabási, A.-L.
- Affiliations
- University of Notre Dame (US)
- Northwestern University (US)
- Department of Physics, University of Notre Dame, Notre Dame, IN 46556, USA.
- Corresponding author
- Oltvai, Z. N.
- ORCID
- Oltvai, Z. N.
- Venue
- Science
- Published
- 2002-08-30
- Volume
- 297
- Issue
- 5586
- Pages
- 1551-1555
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2018045523
- Cited by
- 4,224
- References
- 28
- Citations by year
- 2026: 54 · 2025: 91 · 2024: 109 · 2023: 106 · 2022: 177 · 2021: 194 · 2020: 191 · 2019: 209 · 2018: 214 · 2017: 192 · 2016: 181 · 2015: 200 · 2014: 191 · 2013: 238 · 2012: 209
- FWCI
- 41.03
- Type
- journal article
- Language
- en
- Open access
- green
- arxiv.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Keywords
- metabolic networks, network modularity, hierarchy, topological modules, power-law degree distribution, clustering coefficient, Escherichia coli, cell organization
- MeSH terms
- Escherichia coli, Metabolism, Models, Biological, Systems Theory
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
