Sergei Maslov,¹ Kim Sneppen²

Molecular networks guide the biochemistry of a living cell on multiple levels: Its metabolic and signaling pathways are shaped by the network of interacting proteins, whose production, in turn, is controlled by the genetic regulatory network. To address topological properties of these two networks, we quantified correlations between connectivities of interacting nodes and compared them to a null model of a network, in which all links were randomly rewired. We found that for both interaction and regulatory networks, links between highly connected proteins are systematically suppressed, whereas those between a highly connected and low-connected pairs of proteins are favored. This effect decreases the likelihood of cross talk between different functional modules of the cell and increases the overall robustness of a network by localizing effects of deleterious perturbations.

¹ Department of Physics, Brookhaven National Laboratory, Upton, NY 11973, USA.
² Department of Physics, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.

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Disruption of cerebral networks and cognitive impairment in Alzheimer disease.

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Efficiency of a "Small-World" Brain Network Depends on Consciousness Level: A Resting-State fMRI Study.

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A complex network framework for unbiased statistical analyses of DNA-DNA contact maps.

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Altered Functional Brain Connectivity in a Non-Clinical Sample of Young Adults with Attention-Deficit/Hyperactivity Disorder.

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Abnormal Modular Organization of Functional Networks in Cognitively Impaired Children with Frontal Lobe Epilepsy.

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Topologically Convergent and Divergent Structural Connectivity Patterns between Patients with Remitted Geriatric Depression and Amnestic Mild Cognitive Impairment.

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Diffusion Tensor Tractography Reveals Disrupted Topological Efficiency in White Matter Structural Networks in Multiple Sclerosis.

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Topology of protein interaction network shapes protein abundances and strengths of their functional and nonspecific interactions.

M. Heo, S. Maslov, and E. Shakhnovich (2011)
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Sex- and Brain Size-Related Small-World Structural Cortical Networks in Young Adults: A DTI Tractography Study.

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Discrete Neuroanatomical Networks Are Associated with Specific Cognitive Abilities in Old Age.

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Genome Annotation and Intraviral Interactome for the Streptococcus pneumoniae Virulent Phage Dp-1.

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Nonspecific binding limits the number of proteins in a cell and shapes their interaction networks.

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Diffusion Tensor Tractography Reveals Abnormal Topological Organization in Structural Cortical Networks in Alzheimer's Disease.

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Rewiring of Transcriptional Regulatory Networks: Hierarchy, Rather Than Connectivity, Better Reflects the Importance of Regulators.

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Functional Molecular Ecological Networks.

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Learning to coordinate in complex networks.

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The Spread of Behavior in an Online Social Network Experiment.

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Development of a Large-Scale Functional Brain Network during Human Non-Rapid Eye Movement Sleep.

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A Poisson model for random multigraphs.

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Edge direction and the structure of networks.

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Analysis of lipid pathway genes indicates association of sequence variation near SREBF1/TOM1L2/ATPAF2 with dementia risk.

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Dynamic functional reorganization of the motor execution network after stroke.

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Brain 133, 1224-1238
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Pandora, a PAthway and Network DiscOveRy Approach based on common biological evidence.

K. X. Zhang and B. F. F. Ouellette (2010)
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Age- and Gender-Related Differences in the Cortical Anatomical Network.

G. Gong, P. Rosa-Neto, F. Carbonell, Z. J. Chen, Y. He, and A. C. Evans (2009)
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Pathway identification by network pruning in the metabolic network of Escherichia coli.

P. Gerlee, L. Lizana, and K. Sneppen (2009)
Bioinformatics 25, 3282-3288
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Gene divergence and pathway duplication in the metabolic network of yeast and digital organisms.

P. Gerlee, T. Lundh, B. Zhang, and A. R. A. Anderson (2009)
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Model validation of simple-graph representations of metabolism.

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Coexpression network based on natural variation in human gene expression reveals gene interactions and functions.

R. R. Nayak, M. Kearns, R. S. Spielman, and V. G. Cheung (2009)
Genome Res. 19, 1953-1962
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Scaling properties of European research units.

B. Jamtveit, E. Jettestuen, and J. Mathiesen (2009)
PNAS 106, 13160-13163
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Hub genes with positive feedbacks function as master switches in developmental gene regulatory networks.

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Bioinformatics 25, 1898-1904
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The Complexity of Cell Signaling and the Need for a New Mechanics.

W. S. Hlavacek and J. R. Faeder (2009)
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The building blocks of economic complexity.

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PNAS 106, 10570-10575
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Deciphering Signaling Outcomes from a System of Complex Networks.

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Mapping Anatomical Connectivity Patterns of Human Cerebral Cortex Using In Vivo Diffusion Tensor Imaging Tractography.

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Insights into the Organization of Biochemical Regulatory Networks Using Graph Theory Analyses.

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J. Biol. Chem. 284, 5451-5455
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Ordered cyclic motifs contribute to dynamic stability in biological and engineered networks.

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PNAS 105, 19235-19240
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Network analysis identifies weak and strong links in a metapopulation system.

A. F. Rozenfeld, S. Arnaud-Haond, E. Hernandez-Garcia, V. M. Eguiluz, E. A. Serrao, and C. M. Duarte (2008)
PNAS 105, 18824-18829
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Asymmetric disassembly and robustness in declining networks.

S. Saavedra, F. Reed-Tsochas, and B. Uzzi (2008)
PNAS 105, 16466-16471
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Revealing Modular Architecture of Human Brain Structural Networks by Using Cortical Thickness from MRI.

Z. J. Chen, Y. He, P. Rosa-Neto, J. Germann, and A. C. Evans (2008)
Cereb Cortex 18, 2374-2381
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Cascading failure and robustness in metabolic networks.

A. G. Smart, L. A. N. Amaral, and J. M. Ottino (2008)
PNAS 105, 13223-13228
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Intrinsic Structural Disorder in Adenovirus E1A: a Viral Molecular Hub Linking Multiple Diverse Processes.

P. Pelka, J. N. G. Ablack, G. J. Fonseca, A. F. Yousef, and J. S. Mymryk (2008)
J. Virol. 82, 7252-7263
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Conservation and topology of protein interaction networks under duplication-divergence evolution.

K. Evlampiev and H. Isambert (2008)
PNAS 105, 9863-9868
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Coordinated evolution of the hepatitis C virus.

D. S. Campo, Z. Dimitrova, R. J. Mitchell, J. Lara, and Y. Khudyakov (2008)
PNAS 105, 9685-9690
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GraphWeb: mining heterogeneous biological networks for gene modules with functional significance.

J. Reimand, L. Tooming, H. Peterson, P. Adler, and J. Vilo (2008)
Nucleic Acids Res. 36, W452-W459
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Topological modelling of large networks.

R. J Mondragon (2008)
Phil Trans R Soc A 366, 1931-1940
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Structural Insights into Aberrant Topological Patterns of Large-Scale Cortical Networks in Alzheimer's Disease.

Y. He, Z. Chen, and A. Evans (2008)
J. Neurosci. 28, 4756-4766
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Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction.

S. Lapidus, B. Han, and J. Wang (2008)
PNAS 105, 6039-6044
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Disrupted small-world networks in schizophrenia.

Y. Liu, M. Liang, Y. Zhou, Y. He, Y. Hao, M. Song, C. Yu, H. Liu, Z. Liu, and T. Jiang (2008)
Brain 131, 945-961
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Large-scale screening for novel low-affinity extracellular protein interactions.

K. M. Bushell, C. Sollner, B. Schuster-Boeckler, A. Bateman, and G. J. Wright (2008)
Genome Res. 18, 622-630
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Computing topological parameters of biological networks.

Y. Assenov, F. Ramirez, S.-E. Schelhorn, T. Lengauer, and M. Albrecht (2008)
Bioinformatics 24, 282-284
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Spectrum of genetic diversity and networks of clonal organisms.

A. F Rozenfeld, S. Arnaud-Haond, E. Hernandez-Garcia, V. M Eguiluz, M. A Matias, E. Serrao, and C. M Duarte (2007)
J R Soc Interface 4, 1093-1102
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Susceptible-infected-recovered epidemics in dynamic contact networks.

E. Volz and L. A. Meyers (2007)
Proc R Soc B 274, 2925-2934
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