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Biomolecular Network Structure and Function

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Encyclopedia of Complexity and Systems Science

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Definition of the Subject

Biological research over the past century or so has been dominated by reductionism – identifying and characterizing individual biomolecules – and has enjoyed enormous success. Throughout this history, however, it has become increasingly clear that an individual biomolecule can rarely account for a discrete biological function on its own. A biological process is almost always the result of a complex interplay of relationships among biomolecules (Alon 2003; Bray 2003; Hartwell et al. 1999; Hasty et al. 2002; Kitano 2002; Koonin et al. 2002; Oltvai and Barabasi 2002; Wall et al. 2004), and the treatment of these relationships as a graph is a natural and useful abstraction.

Broadly speaking, a biomolecular networkis a graph representation of relationships (of which there are many types) among a group of biomolecules. Vertices or nodes represent biomolecules, including macromolecules such as genes, proteins, and RNAs, or small biomolecules like amino acids,...

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Abbreviations

Biomolecular network :

A graph representation of relationships among a group of biomolecules. Nodes or vertices represent biomolecules. An edge or link between two vertices indicates a relationship between the corresponding biomolecules, for example, physical interaction, genetic interaction, or regulatory relationship.

Biomolecule :

Any organic molecule that is produced by or essential to a living organism, sometimes specifically referring to macromolecules such as a protein or nucleic acid.

Genetic interaction (epistasis) :

Functional interaction between genes, in which the action of one gene is modified by the other gene, sometimes called the modifier gene. The gene whose phenotype is expressed is said to be epistatic, while the one whose phenotype is altered or suppressed is said to be hypostatic. Epistasis can either refer to this phenomenon or more broadly to any case in which two mutations together cause a phenotype that is surprising given the phenotypes of each single mutation alone.

“Multicolor” network :

A network with edges defined by more than one type of interaction or relationship, with each type corresponding to a different “color.”

Network motif :

A specific pattern of connected vertices and edges that occurs frequently within a given network.

Power-law network :

A network defined by a degree distribution which follows \( P(k)\sim {k}^{-\gamma } \), where the probability P(k) that a vertex in the network connects with k other vertices is roughly proportional to k −γ. Sometimes networks that exhibit this behavior only at high degree are also called power law. The coefficient γ seems to vary approximately between 2 and 3 for most real networks. In a power-law network, majority of the vertices have low degree (connectivity), while a small fraction of the vertices have very high degree. Highly connected vertices are referred to as hubs.

Protein-protein interaction :

The physical association of two protein molecules with each other. A pair of proteins can interact directly with physical contact or indirectly through other biomolecules, often other proteins.

Scale-free network :

See power-law network.

“Single-color” network :

A network with edges defined by only one type of interaction or relationship.

Small-world network :

A special type of network with (1) short characteristic path length, such that most vertex pairs are connected to one another via only a small number of edges, and (2) high clustering coefficient, such that neighbors of a given vertex tend to be connected to one another.

Yeast two-hybrid :

An experimental method to examine protein-protein interaction, in which one protein is fused to a transcriptional activation domain (the GAL4 activation domain) and the other to a DNA-binding domain (the GAL4 DNA-binding domain), and both fusion proteins are introduced into yeast. Expression of a GAL4-regulated reporter gene with the appropriate DNA-binding sites upstream of its promoter indicates that the two proteins physically interact.

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  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    Lan V. Zhang & Frederick P. Roth

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Zhang, L.V., Roth, F.P. (2015). Biomolecular Network Structure and Function. In: Meyers, R. (eds) Encyclopedia of Complexity and Systems Science. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27737-5_38-3

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