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Network biology: understanding the cell's functional organization

Nature Reviews Genetics volume 5, pages 101–113 (2004)Cite this article

Key Points

  • The emergence of new, high-throughput data-collection techniques increasingly allows us to simultaneously interrogate the status of a cell's components and to determine how and when these molecules interact with each other.

  • Various types of molecular interaction webs (including protein–protein interaction, metabolic, signaling and transcription-regulatory networks) emerge from the sum of these interactions that together are principal determinants of the system-scale behaviour of the cell.

  • A major challenge of contemporary biology is to embark on an integrated theoretical and experimental programme to map out, understand and model in quantifiable terms the topological and dynamical properties of the various networks that control the behaviour of the cell.

  • Here, we review the present knowledge of the design principles for the structure and system-scale function of cellular networks, and the evolutionary mechanisms that might have shaped their development.

  • A key insight is that the architectural features of molecular interaction networks within a cell are shared to a large degree by other complex systems, such as the Internet, computer chips or society. This unexpected universality suggests that similar laws govern the development and function of most complex networks in nature.

  • Providing that sufficient formalism will be developed this new conceptual framework could potentially revolutionize our view and practice of molecular cell biology.

Abstract

A key aim of postgenomic biomedical research is to systematically catalogue all molecules and their interactions within a living cell. There is a clear need to understand how these molecules and the interactions between them determine the function of this enormously complex machinery, both in isolation and when surrounded by other cells. Rapid advances in network biology indicate that cellular networks are governed by universal laws and offer a new conceptual framework that could potentially revolutionize our view of biology and disease pathologies in the twenty-first century.

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Figure 1: Characterizing metabolic networks.
Figure 2: Yeast protein interaction network.
Figure 3: The origin of the scale-free topology and hubs in biological networks.

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Acknowledgements

We thank two anonymous reviewers for their comments and M. Vidal for sharing unpublished work. This research was supported by grants from the National Institutes of Health, Department of Energy (to A.-L.B. and Z.N.O.) and the National Science Foundation (to A.-L.B.)

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Authors and Affiliations

  1. Department of Physics, University of Notre Dame, Notre Dame, 46556, Indiana, USA

    Albert-László Barabási

  2. Department of Pathology, Northwestern University, Chicago, 60611, Illinois, USA

    Zoltán N. Oltvai

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Self-organized networks

Glossary

PROTEIN CHIPS

Similar to cDNA microarrays, this evolving technology involves arraying a genomic set of proteins on a solid surface without denaturing them. The proteins are arrayed at a high enough density for the detection of activity, binding to lipids and so on.

YEAST TWO-HYBRID SCREEN

A genetic approach for the identification of potential protein–protein interactions. Protein X is fused to the site-specific DNA-binding domain of a transcription factor and protein Y to its transcriptional-activation domain — interaction between the proteins reconstitutes transcription-factor activity and leads to expression of reporter genes with recognition sites for the DNA-binding domain.

microRNA

A class of small, non-coding RNAs that are important for development and cell homeostasis, with possible roles in several human disease pathologies.

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Barabási, AL., Oltvai, Z. Network biology: understanding the cell's functional organization. Nat Rev Genet 5, 101–113 (2004). https://doi.org/10.1038/nrg1272

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