Bow ties, metabolism and disease
Abstract
Highly organized, universal structures underlying biological and technological networks mediate effective trade-offs among efficiency, robustness and evolvability, with predictable fragilities that can be used to understand disease pathogenesis. The aims of this article are to describe the features of one common organizational architecture in biology, the bow tie. Large-scale organizational frameworks such as the bow tie are necessary starting points for higher-resolution modeling of complex biologic processes
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
The metabolic and dopamine systems are examples of nested layered architectures in which the dopamine bowtie subserves internal signals mediated by hypothalamic signaling.
“These two systems can be viewed as examples of nested layered architectures (111), in which the DA bowtie subserves the internal signals mediated by hypothalamic signaling (Figure 2C).”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [111]
The human brain is organized as a layered architecture of interactive networks, sometimes called a bowtie, in which many inputs converge onto a small number of processes and then fan out into diverse outputs.
“The human brain is a complex biological system that is organized in the layered architecture of interactive networks, sometimes called bowtie (111), whereby a narrowing funnel of many potential inputs converges onto a relatively small number of processes before fanning out again into a diversity of outputs.”
From The Addictive Dimensionality of Obesity (2013) · cites this paper as [111]
Cites
Reverse engineering of biological complexity
Csete, M. E., & Doyle, J. C. (2002) · Science · doi:10.1126/science.1069981 · Cited by 1,215 · see citing works
Self-citationCarlson, J. M., & Doyle, J. C. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.012582499 · Cited by 815 · see citing works
Self-citationMetabolic network structure determines key aspects of functionality and regulation
Stelling, J., Klamt, S., Bettenbrock, K., Schuster, S., & Gilles, E. D. (2002) · Nature · doi:10.1038/nature01166 · Cited by 802 · see citing works
Low, S. H., Paganini, F., & Doyle, J. C. (2002) · IEEE Control Systems · doi:10.1109/37.980245 · Cited by 798 · see citing works
Self-citationBiological networks: the tinkerer as an engineer
Alon, U. (2003) · Science · doi:10.1126/science.1089072 · Cited by 706 · see citing works
Gerhart, J. C., & Kirschner, M. W. (1997) · Cited by 437 · 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
McVean, G. T. (1997) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(97)89823-4 · Cited by 394 · see citing works
The connectivity structure, giant strong component and centrality of metabolic networks
Ma, H., & Zeng, A. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg177 · Cited by 391 · see citing works
Ptashne, M., & Gann, A. A. F. (2001) · Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) · Cited by 356 · 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
Design of gene circuits: lessons from bacteria
Wall, M. E., Hlavacek, W. S., & Savageau, M. A. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1244 · Cited by 228 · see citing works
Building with a scaffold: emerging strategies for high- to low-level cellular modeling
Ideker, T. E., & Lauffenburger, D. A. (2003) · Trends in biotechnology · doi:10.1016/s0167-7799(03)00115-x · Cited by 180 · see citing works
Caporale, L. H. (2003) · Annual Review of Microbiology · doi:10.1146/annurev.micro.57.030502.090855 · Cited by 77 · see citing works
On the complete determination of biological systems
Selinger, D. W., Wright, M. A., & Church, G. M. (2003) · Trends in biotechnology · doi:10.1016/s0167-7799(03)00113-6 · Cited by 49 · see citing works
Unveiling steady‐state multiplicity in hybridoma cultures: The cybernetic approach
Namjoshi, A. A., Hu, W., & Ramkrishna, D. (2002) · Biotechnology and Bioengineering · doi:10.1002/bit.10447 · Cited by 41 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Inflammaging: a new immune–metabolic viewpoint for age-related diseases
Franceschi, C., Garagnani, P., Parini, P., Giuliani, C., & Santoro, A. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0059-4 · Cited by 3,586 · see citing works
Kitano, H. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1471 · Cited by 2,278 · see citing works
The Language of Calcium Signaling
Dodd, A. N., Kudla, J., & Sanders, D. (2010) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-070109-104628 · Cited by 1,328 · 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
Self-citationCrisis management in hindsight: Cognition, communication, coordination, and control
Comfort, L. K. (2007) · Public Administration Review · doi:10.1111/j.1540-6210.2007.00827.x · Cited by 940 · see citing works
Towards a theory of biological robustness
Kitano, H. (2007) · Molecular Systems Biology · doi:10.1038/msb4100179 · Cited by 803 · see citing works
Obesity and addiction: Neurobiological overlaps
Volkow, N. D., Wang, G. ‐., Tomasi, D., & Baler, R. D. (2013) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.01031.x · Cited by 800 · see citing works
Adverse Outcome Pathway (AOP) Development I: Strategies and Principles
Villeneuve, D. L., Crump, D., García‐Reyero, N., Hecker, M., Hutchinson, T. H., LaLone, C. A., Landesmann, B., Lettieri, T., Munn, S., Malgorzata, N., et al. (2014) · Toxicological Sciences · doi:10.1093/toxsci/kfu199 · Cited by 733 · see citing works
Metabolic networks in motion: 13C‐based flux analysis
Sauer, U. (2006) · Molecular Systems Biology · doi:10.1038/msb4100109 · Cited by 664 · see citing works
The protein corona from nanomedicine to environmental science
Mahmoudi, M., Landry, M. P., Moore, A. V., & Coreas, R. (2023) · Nature Reviews Materials · doi:10.1038/s41578-023-00552-2 · Cited by 659 · see citing works
Cortical high-density counterstream architectures
Markov, N. T., Ercsey-Ravasz, M., Van Essen, D. C., Knoblauch, K., Toroczkai, Z., & Kennedy, H. (2013) · Science · doi:10.1126/science.1238406 · Cited by 616 · see citing works
Bruggeman, F. J., & Westerhoff, H. V. (2006) · Trends in Microbiology · doi:10.1016/j.tim.2006.11.003 · Cited by 532 · see citing works
The “robust yet fragile” nature of the Internet
Doyle, J. C., Alderson, D., Li, L., Low, S. H., Roughan, M., Shalunov, S., Tanaka, R., & Willinger, W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501426102 · Cited by 475 · see citing works
Self-citationA robustness-based approach to systems-oriented drug design
Kitano, H. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2195 · Cited by 488 · see citing works
Bhattacharyya, R. P., Reményi, A., Yeh, B. J., & Lim, W. A. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.103004.142710 · Cited by 449 · see citing works
The 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
The theory of facilitated variation
Gerhart, J. C., & Kirschner, M. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701035104 · Cited by 404 · see citing works
Currin, A., Swainston, N., Day, P. J., & Kell, D. B. (2014) · Chemical Society Reviews · doi:10.1039/c4cs00351a · Cited by 383 · see citing works
The Addictive Dimensionality of Obesity
Volkow, N. D., Wang, G.-J., Tomasi, D., & Baler, R. D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.020 · Cited by 380 · see citing works
Structure and dynamics of core/periphery networks
Csermely, P., London, A., Wu, L.-Y., & Uzzi, B. (2013) · Journal of Complex Networks · doi:10.1093/comnet/cnt016 · Cited by 434 · see citing works
Kell, D. B. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0577-x · Cited by 361 · see citing works
Structure and dynamics of core-periphery networks
Csermely, P., London, A., Wu, L. Y., & Uzzi, B. (2013) · Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) · Cited by 361 · see citing works
A Logical Model Provides Insights into T Cell Receptor Signaling
Saez-Rodriguez, J., Simeoni, L., Lindquist, J. A., Hemenway, R., Bommhardt, U., Arndt, B., Haus, U.-U., Weismantel, R., Gilles, E. D., Klamt, S., et al. (2007) · PLoS Computational Biology · doi:10.1371/journal.pcbi.0030163 · Cited by 352 · see citing works
A comprehensive map of the toll‐like receptor signaling network
Oda, K., & Kitano, H. (2006) · Molecular Systems Biology · doi:10.1038/msb4100057 · Cited by 354 · see citing works
Prabakaran, S., Lippens, G., Steen, H., & Gunawardena, J. (2012) · WIREs Systems Biology and Medicine · doi:10.1002/wsbm.1185 · Cited by 335 · see citing works
Fischer, E., & Sauer, U. (2005) · Nature Genetics · doi:10.1038/ng1555 · Cited by 318 · see citing works
Growth control of the eukaryote cell: a systems biology study in yeast
Castrillo, J. I., Zeef, L. A., Hoyle, D. C., Zhang, N., Hayes, A., Gardner, D. C., Cornell, M. J., Petty, J., Hakes, L., Wardleworth, L., et al. (2007) · Journal of Biology · doi:10.1186/jbiol54 · Cited by 263 · see citing works
Toward the dynamic interactome: it's about time
Przytycka, T. M., Singh, M., & Slonim, D. K. (2010) · Briefings in Bioinformatics · doi:10.1093/bib/bbp057 · Cited by 252 · see citing works
RISK, SECURITY, AND DISASTER MANAGEMENT
Comfort, L. K. (2005) · Annual Review of Political Science · doi:10.1146/annurev.polisci.8.081404.075608 · Cited by 254 · see citing works
A comprehensive map of the mTOR signaling network
Caron, É., Ghosh, S., Matsuoka, Y., Ashton‐Beaucage, D., Therrien, M., Lemieux, S., Perreault, C., Roux, P. P., & Kitano, H. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.108 · Cited by 241 · see citing works
Metabolic functions of duplicate genes in Saccharomyces cerevisiaePreprint
Kuepfer, L., Sauer, U., & Blank, L. M. (2005) · Genome Research · doi:10.1101/gr.3992505 · Cited by 238 · see citing works
NOW vs LATER brain circuits: implications for obesity and addiction
Volkow, N. D., & Baler, R. D. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.04.002 · Cited by 237 · see citing works
Large-scale reconstruction and phylogenetic analysis of metabolic environments
Borenstein, E., Kupiec, M., Feldman, M. W., & Ruppin, E. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806162105 · Cited by 238 · see citing works
Revisiting “scale-free” networks
Keller, E. F. (2005) · BioEssays · doi:10.1002/bies.20294 · Cited by 233 · see citing works
A complex systems approach to aging biology
Cohen, A. A., Ferrucci, L., Fülöp, T., Gravel, D., Hao, N., Kriete, A., Levine, M. E., Lipsitz, L. A., Olde Rikkert, M. G. M., Rutenberg, A., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00252-6 · Cited by 221 · see citing works
A comprehensive functional analysis of tissue specificity of human gene expression
Dezső, Z., Nikolsky, Y., Sviridov, E., Shi, W., Serebriyskaya, T., Dosymbekov, D., Bugrim, A. E., Rakhmatulin, E. A., Brennan, R., Guryanov, A., et al. (2008) · BMC Biology · doi:10.1186/1741-7007-6-49 · Cited by 213 · see citing works
Inflammaging: Implications in Sarcopenia
Antuña, E., Cachán-Vega, C., Bermejo-Millo, J. C., Potes, Y., Caballero, B., Vega‐Naredo, I., Coto‐Montes, A. M., & García-González, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315039 · Cited by 223 · see citing works
The Origin and Nature of Life on Earth: The Emergence of the Fourth Geosphere
Smith, E., & Morowitz, H. J. (2016) · doi:10.1017/cbo9781316348772 · Cited by 215 · see citing works
Functioning of a metabolic flux sensor in <i>Escherichia coli</i>
Kochanowski, K., Volkmer, B., Gerosa, L., Haverkorn van Rijsewijk, B. R., Schmidt, A., & Heinemann, M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1202582110 · Cited by 196 · see citing works
Recurrent Circuitry for Balancing Sleep Need and Sleep
Donlea, J. M., Pimentel, D. O., Talbot, C. B., Kempf, A., Omoto, J. J., Hartenstein, V., & Miesenböck, G. (2018) · Neuron · doi:10.1016/j.neuron.2017.12.016 · Cited by 212 · see citing works
Environmental variability and modularity of bacterial metabolic networks
Parter, M., Kashtan, N., & Alon, U. S. (2007) · BMC Evolutionary Biology · doi:10.1186/1471-2148-7-169 · Cited by 201 · see citing works
Imai, S. (2009) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-008-9041-4 · Cited by 200 · see citing works
Millan, M. J. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.10.039 · Cited by 197 · see citing works
Woody, E. Z., & Szechtman, H. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.08.003 · Cited by 195 · see citing works
Human models of aging and longevity
Cevenini, E., Invidia, L., Lescai, F., Salvioli, S., Tieri, P., Castellani, G., & Franceschi, C. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.8.9.1393 · Cited by 195 · see citing works
Current prospects for mRNA gene delivery
Yamamoto, A., Kormann, M., Rosenecker, J., & Rudolph, C. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.09.016 · Cited by 193 · see citing works
Biological Robustness: Paradigms, Mechanisms, and Systems Principles
Whitacre, J. M. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00067 · Cited by 182 · see citing works
Common effector processing mediates cell-specific responses to stimuli
Miller‐Jensen, K., Janes, K. A., Brugge, J. S., & Lauffenburger, D. A. (2007) · Nature · doi:10.1038/nature06001 · Cited by 191 · see citing works
GDF15, an emerging key player in human aging
Conte, M., Giuliani, C., Chiariello, A., Iannuzzi, V., Franceschi, C., & Salvioli, S. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101569 · Cited by 189 · see citing works
Stratified medicine for mental disorders
Schumann, G., Binder, E. B., Holte, A., de Kloet, E. R., Oedegaard, K. J., Robbins, T. W., Walker-Tilley, T. R., Bitter, I., Brown, V. J., Buitelaar, J., et al. (2014) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.09.010 · Cited by 186 · see citing works
Wiltschi, B., Cernava, T., Dennig, A., Casas, M. G., Geier, M., Gruber, S., Haberbauer, M., Heidinger, P., Acero, E. H., Kratzer, R., et al. (2020) · Biotechnology Advances · doi:10.1016/j.biotechadv.2020.107520 · Cited by 182 · see citing works
Architecture, constraints, and behavior
Doyle, J. C., & CSETE, M. E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103557108 · Cited by 179 · see citing works
Self-citationStress-Induced Mutagenesis: Implications in Cancer and Drug Resistance
Fitzgerald, D. M., Hastings, P. J., & Rosenberg, S. M. (2016) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-050216-121919 · Cited by 174 · see citing works
Dunn, W. B., Broadhurst, D., Deepak, S. M., Buch, M. H., McDowell, G., Spasić, ., Ellis, D. I., Brooks, N. H., Kell, D. B., & Neyses, L. (2007) · Metabolomics · doi:10.1007/s11306-007-0063-5 · Cited by 174 · see citing works
Contrasting Views of Complexity and Their Implications For Network-Centric Infrastructures
Alderson, D., & Doyle, J. C. (2010) · IEEE Transactions on Systems Man and Cybernetics - Part A Systems and Humans · doi:10.1109/tsmca.2010.2048027 · Cited by 169 · see citing works
Self-citationChallenging homeostasis to define biomarkers for nutrition related health
van Ommen, B., Keijer, J., Heil, S. G., & Kaput, J. (2009) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200800390 · Cited by 167 · see citing works
Tanaka, R. J. (2005) · Physical Review Letters · doi:10.1103/physrevlett.94.168101 · Cited by 147 · see citing works
Robustness trade‐offs and host–microbial symbiosis in the immune system
Kitano, H., & Oda, K. (2006) · Molecular Systems Biology · doi:10.1038/msb4100039 · Cited by 145 · see citing works
Oxytocin׳s role in anxiety: A critical appraisal
MacDonald, K., & Feifel, D. (2014) · Brain Research · doi:10.1016/j.brainres.2014.01.025 · Cited by 139 · see citing works
Amit, I., Wides, R., & Yarden, Y. (2007) · Molecular Systems Biology · doi:10.1038/msb4100195 · Cited by 144 · see citing works
<i>Concepts and Mechanisms of Generalized Central Nervous System Arousal</i>
Pfaff, D., Ribeiro, A., Matthews, J., & Kow, L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1417.019 · Cited by 129 · see citing works
The Compositional and Evolutionary Logic of Metabolism
Braakman, R., & Smith, E. (2012) · Physical Biology · doi:10.1088/1478-3975/10/1/011001 · Cited by 158 · 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
Pocklington, A. J., Cumiskey, M. A., Armstrong, J. D., & Grant, S. G. N. (2006) · Molecular Systems Biology · doi:10.1038/msb4100041 · Cited by 130 · see citing works
Process intensification in the future production of base chemicals from biomass
Sanders, J. P. M., Clark, J. H., Harmsen, G. J., Heeres, H. J., Heijnen, J. J., Kersten, S. R. A., Swaaij, W. P. M. V., & Moulijn, J. A. (2011) · Chemical Engineering and Processing - Process Intensification · doi:10.1016/j.cep.2011.08.007 · Cited by 129 · see citing works
Integrating Cellular Metabolism into a Multiscale Whole-Body Model
Krauß, M., Schaller, S., Borchers, S., Findeisen, R., Lippert, J., & Kuepfer, L. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002750 · Cited by 123 · see citing works
Zhang, C., Taylor, B. E., Ourthiague, D., & Hoffmann, A. (2015) · Science Signaling · doi:10.1126/scisignal.aaa5208 · Cited by 123 · see citing works
Evolution of Bow-Tie Architectures in Biology
Friedlander, T., Mayo, A., Tlusty, T., & Alon, U. S. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004055 · Cited by 119 · see citing works
Hansen, A. S., & O’Shea, E. K. (2015) · eLife · doi:10.7554/elife.06559 · Cited by 113 · see citing works
A taxonomy of biologically inspired research in computer networking
Meisel, M., Pappas, V., & Zhang, L. (2009) · Computer Networks · doi:10.1016/j.comnet.2009.08.022 · Cited by 118 · see citing works
Lüdtke, N., Panzeri, S., Brown, M., Broomhead, D. S., Knowles, J. D., Montemurro, M. A., & Kell, D. B. (2007) · Journal of The Royal Society Interface · doi:10.1098/rsif.2007.1079 · Cited by 116 · see citing works
Stover, P. J., & Caudill, M. A. (2008) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2008.06.430 · Cited by 116 · see citing works
An architectural view of game theoretic control
Gopalakrishnan, R., Marden, J. R., & Wierman, A. (2011) · ACM SIGMETRICS Performance Evaluation Review · doi:10.1145/1925019.1925026 · Cited by 110 · see citing works
The Functional Structure of Central Carbon Metabolism in Pseudomonas putida KT2440
Sudarsan, S., Dethlefsen, S., Blank, L. M., Siemann‐Herzberg, M., & Schmid, A. (2014) · Applied and Environmental Microbiology · doi:10.1128/aem.01643-14 · Cited by 108 · see citing works
The molecular basis of targeting protein kinases in cancer therapeutics
Tsai, C., & Nussinov, R. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.04.001 · Cited by 90 · see citing works
Redesigning metabolism based on orthogonality principles
Pandit, A. V., Srinivasan, S., & Mahadevan, R. (2017) · Nature Communications · doi:10.1038/ncomms15188 · Cited by 90 · see citing works
New surveyor tools for charting microbial metabolic maps
Rainer Breitling, A., Vitkup, D., & Barrett, M. P. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1797 · Cited by 89 · see citing works
An orthogonal metabolic framework for one-carbon utilization
Chou, A., Lee, S. H., Zhu, F., Clomburg, J. M., & González, R. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00453-0 · Cited by 87 · see citing works
Tieri, P., Grignolio, A., Zaikin, A. A., Mishto, M., Remondini, D., Castellani, G., & Franceschi, C. (2010) · Theoretical Biology and Medical Modelling · doi:10.1186/1742-4682-7-32 · Cited by 86 · see citing works
Future systems and control research in synthetic biology
Vecchio, D. D., Qian, Y., Murray, R. M., & Sontag, E. D. (2018) · Annual Reviews in Control · doi:10.1016/j.arcontrol.2018.04.007 · Cited by 88 · see citing works
STRESS PROTEIN EXPRESSION KINETICS
Diller, K. R. (2006) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.7.060804.100449 · Cited by 86 · see citing works
Pritchard, L., & Birch, P. R. J. (2010) · Plant Science · doi:10.1016/j.plantsci.2010.12.008 · Cited by 85 · see citing works
Growth chart curves do not describe individual growth biology
Lampl, M., & Thompson, A. L. (2007) · American Journal of Human Biology · doi:10.1002/ajhb.20707 · Cited by 84 · see citing works
Theoretical and experimental analysis links isoform-specific ERK signalling to cell fate decisions
Schilling, M., Maiwald, T., Hengl, S., Winter, D., Kreutz, C., Kolch, W., Lehmann, W. D., Timmer, J., & Klingmüller, U. (2009) · Molecular Systems Biology · doi:10.1038/msb.2009.91 · Cited by 79 · see citing works
Response diversity as a sustainability strategy
Walker, B., Crépin, A., Nyström, M., Anderies, J. M., Andersson, E., Elmqvist, T., Queiroz, C., Barrett, S. A., Bennett, E. M., Cárdenas, J.-C., et al. (2023) · Nature Sustainability · doi:10.1038/s41893-022-01048-7 · Cited by 84 · see citing works
Ma, A., & Mondragón, R. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119678 · Cited by 79 · see citing works
Niethammer, P. (2016) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2016.05.001 · Cited by 78 · see citing works
The evolution of layered protocol stacks leads to an hourglass-shaped architecture
Akhshabi, S., & Dovrolis, C. (2011) · ACM SIGCOMM Conference (SIGCOMM) · doi:10.1145/2018436.2018460 · Cited by 78 · see citing works
Epigenomics and the concept of degeneracy in biological systems
Maleszka, R., Mason, P. H., & Barron, A. B. (2013) · Briefings in Functional Genomics · doi:10.1093/bfgp/elt050 · Cited by 77 · see citing works
Drought rewires the cores of food webs
Lu, X., Gray, C., Brown, L. E., Ledger, M. E., Milner, A. M., Mondragón, R. J., Woodward, G., & Ma, A. (2016) · Nature Climate Change · doi:10.1038/nclimate3002 · Cited by 77 · see citing works
Samarin, J., Laketa, V., Malz, M., Roessler, S. K., Stein, I., Horwitz, E. P., Singer, S., Dimou, E., Cigliano, A., Bissinger, M., et al. (2015) · Hepatology · doi:10.1002/hep.28357 · Cited by 76 · see citing works
Computational Models of Metabolism: Stability and Regulation in Metabolic Networks
Steuer, R., & Junker, B. H. (2008) · Advances in chemical physics · doi:10.1002/9780470475935.ch3 · Cited by 76 · see citing works
Evolutionary Remodeling of Bacterial Motility Checkpoint Control
Ni, B., Ghosh, B., Páldy, F. S., Colin, R., Heimerl, T., & Sourjik, V. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.088 · Cited by 74 · see citing works
Charting the NF-κB Pathway Interactome Map
Tieri, P., Termanini, A., Bellavista, E., Salvioli, S., Capri, M., & Franceschi, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032678 · Cited by 73 · see citing works
An efficient and exact stochastic simulation method to analyze rare events in biochemical systems
Kuwahara, H., & Mura, I. (2008) · The Journal of Chemical Physics · doi:10.1063/1.2987701 · Cited by 73 · see citing works
Reconstruction, modeling & analysis of Halobacterium salinarum R-1metabolism
Gonzalez, O., von Gronau, S., Falb, M., Pfeiffer, F., Mendoza, E., Zimmer, R., & Oesterhelt, D. (2007) · Molecular BioSystems · doi:10.1039/b715203e · Cited by 71 · see citing works
Modular co-evolution of metabolic networks
Zhao, J., Ding, G., Tao, L., Yu, H. J., Yu, Z., Luo, J., Cao, Z., & Li, Y. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-311 · Cited by 70 · see citing works
Tota, B., Cerra, M. C., & Gattuso, A. (2010) · Journal of Experimental Biology · doi:10.1242/jeb.027391 · Cited by 69 · see citing works
Integrated cellular network of transcription regulations and protein-protein interactions
Wang, Y., & Chen, B. (2010) · BMC Systems Biology · doi:10.1186/1752-0509-4-20 · Cited by 68 · see citing works
- Authors
- Csete, M., & Doyle, J.
- Affiliations
- Emory University (US)
- California Institute of Technology (US)
- Corresponding author
- Csete, Marie
- Doyle, John
- Venue
- Trends in biotechnology
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 22
- Issue
- 9
- Pages
- 446-450
- ISSN
- 0167-7799 (ISSN-L)
- OpenAlex
- W2120661262
- Cited by
- 468
- References
- 16
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 11 · 2023: 17 · 2022: 16 · 2021: 21 · 2020: 10 · 2019: 21 · 2018: 39 · 2017: 12 · 2016: 20 · 2015: 17 · 2014: 22 · 2013: 20 · 2012: 33
- FWCI
- 8.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P01 AG-20591, P01AG020591)
- Exploratory Research for Advanced Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- 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
- Keywords
- biological networks, network organization, metabolic networks, pathogenesis, network fragility, robustness, evolvability, efficiency-robustness trade-off
- MeSH terms
- Diabetes Mellitus, Disease, Glucose, Homeostasis, Metabolism, Models, Biological, Nutritional Physiological Phenomena, Computational Biology, Systems Biology
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
