# Network motifs: simple building blocks of complex networks.

@article{Milo2002NetworkMS, title={Network motifs: simple building blocks of complex networks.}, author={Ron Milo and Shai S. Shen-Orr and Shalev Itzkovitz and Nadav Kashtan and Dmitri B. Chklovskii and Uri Alon}, journal={Science}, year={2002}, volume={298 5594}, pages={ 824-7 } }

Complex networks are studied across many fields of science. [... ] Key Result We found such motifs in networks from biochemistry, neurobiology, ecology, and engineering. The motifs shared by ecological food webs were distinct from the motifs shared by the genetic networks of Escherichia coli and Saccharomyces cerevisiae or from those found in the World Wide Web. Expand

## 6,330 Citations

Network motif identification in stochastic networks.

- BiologyProceedings of the National Academy of Sciences of the United States of America
- 2006

A finite mixture model for stochastic networks is established and an expectation-maximization algorithm is developed for identifying Stochastic network motifs derived from families of mutually similar but not necessarily identical patterns of interconnections.

Topological generalizations of network motifs.

- Computer SciencePhysical review. E, Statistical, nonlinear, and soft matter physics
- 2004

Using mathematical modeling, a systematic approach is presented to define "motif generalizations": families of motifs of different sizes that share a common architectural theme in transcription, neuronal, and electronic networks.

Formal Analysis of Network Motifs Links Structure to Function in Biological Programs

- Biology, Computer ScienceIEEE/ACM Transactions on Computational Biology and Bioinformatics
- 2021

This work demonstrates the scalability and biological relevance of the approach by studying the previously defined networks governing myeloid differentiation, the yeast cell cycle, and naïve pluripotency in mouse embryonic stem cells, revealing the requirement for certain motifs in these systems.

Emergence of dynamic properties in network hypermotifs.

- Computer ScienceProceedings of the National Academy of Sciences of the United States of America
- 2022

This framework provides a basis for exploring the mesoscale structure and behavior of complex systems where it can be used to reveal intermediate patterns in complex networks and to identify specific nodes and links in the network that are the key drivers of the network's emergent properties.

Organisation of feed-forward loop motifs reveals architectural principles in natural and engineered networks

- BiologybioRxiv
- 2017

It is shown how this information can be used to effectively predict functionally important nodes in the metabolic network of Escherichia coli and have implications for understanding how networked systems are constructed from motif parts and elucidates constraints that guide their evolution.

On motifs and functional modules in complex networks

- Biology2009 IEEE Toronto International Conference Science and Technology for Humanity (TIC-STH)
- 2009

It is argued that the over-representation of motifs arises not because motifs are fundamental network fragments, but as a result of predesigned basic functional modules consisting of motif-clusters, and cross-module connections involving buses in the circuits and global regulators in the transcriptional regulatory network.

An Algorithm to Construct Network Motifs for Bioinformatics Study

- Computer Science, Mathematics
- 2019

This paper proposes a systematic method which can generate all the allowed network motifs without bipartite, isolated and isomorphic motifs and illustrated its approach by applying it to generate the complete sets of both 3-node-motifs and 4- node-Motifs.

Organization of feed-forward loop motifs reveals architectural principles in natural and engineered networks

- Computer ScienceScience Advances
- 2018

Methods to decipher the rules controlling how small structures cluster and connect in complex networks are developed and shown how this information can be used to effectively predict functionally important nodes in the metabolic network of Escherichia coli.

In Search of the Biological Significance of Modular Structures in Protein Networks

- BiologyPLoS Comput. Biol.
- 2007

Using computer simulation, it is demonstrated that a higher-than-expected modularity can arise during network growth through a simple model of gene duplication, without natural selection for modularity.

Recurrent Structural Motifs Reflect Characteristics of Distinct Networks

- Computer Science2012 IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining
- 2012

The method from Milo et al. 2002 is modified and improved to detect significantly enriched motifs in both directed and undirected networks and reveals the nature of distinct types of networks.

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