Network motif

By definition, Network motifs are patterns that occur in different parts of a network at frequencies much higher than those found in randomized networks. This new concept is introduced by Uri Alon and his group members to detect basic building blocks of all complex networks^[1], with a special focus on gene regulatory networks^[2]. It has been shown later that this idea can be used to explain conserved patterns in other biological networks, like protein-protein interaction networks, signal transduction networks and metabolic networks^[3][4][5].

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Well-known motifs

  Different studies have shown that certain motifs are found frequently in the biological networks. The simplest possible motif in a regulatory network is the autoregulation motif, in which a certain species up-regulates or down-regulates its own expression/activity. It has been shown that this motif appears at least 40 times in the E. coli regulatory network^[6], which is much greater than what is expected by chance.   Another important network motif is feed-forward motif (or feed-forward loop)^[7], which consists of three species, so that the first one influences the third one indirectly via the second one, while it is also possible to influence it directly. Because each of the three interactions can be either activation or inhibition, totally eight possible feed-forward motifs can be imagined. Interestingly, some of these possible motifs are under-represented in gene regulatory networks, while the others are over-represented.

It is generally believed that each type of the conserved motifs shows a specific function^[6]. For example, four of the eight feed-forward loops are sign-sensitive accelerators, i.e. they speed up the response in off-to-on direction, but not in on-to-off direction^[7]. However, some authors have recently argued that some motifs, like bi-fan motifs, might show a variety depending on the conditions, and therefore^[8], structure of the motif does not necessarily determine function.

References

1. ^ Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U. Network motifs: simple building blocks of complex networks. Science. 2002 ;298(5594):824-7. Entrez PubMed 12399590
2. ^ Shen-Orr SS, Milo R, Mangan S, Alon U. Network motifs in the transcriptional regulation network of Escherichia coli. Nature Genet. 2002 May;31(1):64-8. Entrez PubMed 11967538
3. ^ Koschützki D, Schwöbbermeyer H, Schreiber F.Ranking of network elements based on functional substructures. J. Theor. Biol. 2007, 248(3):471-9. Entrez PubMed 17644116
4. ^ Yeger-Lotem E, Sattath S, Kashtan N, Itzkovitz S, Milo R, Pinter RY, Alon U, Margalit H.Network motifs in integrated cellular networks of transcription-regulation and protein-protein interaction. Proc. Natl. Acad. Sci. USA. 2004;101(16):5934-9. Entrez PubMed 15079056
5. ^ Eom YH, Lee S, Jeong H. Exploring local structural organization of metabolic networks using subgraph patterns. J. Theor. Biol. 2006;241(4):823-9. Entrez PubMed 16504210
6. ^ ^{a b} Alon U. An Introduction to Systems Biology: Design Principles of Biological Circuits, Chapman & Hall/CRC, 2006, ISBN 1584886420
7. ^ ^{a b} Mangan S., Alon U. Structure and function of the feed-forward loop network motif. Proc. Natl. Acad. Sci. USA. 2003;100(21): 11980-5. Entrez PubMed 14530388
8. ^ Ingram P.J., Stumpf M.P., Stark J. Network motifs: structure does not determine function. BMC Genomics. 2006; 7: 108.Entrez PubMed 16677373

External links

Uri Alon's web page