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

Thomas E. Gorochowski*, Claire S. Grierson, Mario Di Bernardo

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

34 Citations (Scopus)
179 Downloads (Pure)


Network motifs are significantly overrepresented subgraphs that have been proposed as building blocks for natural and engineered networks. Detailed functional analysis has been performed for many types of motif in isolation, but less is known about how motifsworktogetherto perform complextasks. To addressthis issue, we measurethe aggregation of network motifs via methods that extract precisely how these structures are connected. Applying this approach to a broad spectrum of networked systems and focusing on the widespread feed-forward loop motif, we uncover striking differences in motif organization. The types of connection are often highly constrained, differ between domains, and clearly capture architectural principles. We show how this information can be used to effectively predict functionally important nodes in the metabolic network of Escherichia coli. Our findings have implications for understanding how networked systems are constructed from motif parts and elucidate constraints that guide their evolution.

Original languageEnglish
Article numbereaap9751
Number of pages14
JournalScience Advances
Issue number3
Publication statusPublished - 28 Mar 2018

Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio


  • networks
  • complex systems
  • motifs
  • clustering
  • feed-forward loop
  • systems biology
  • synthetic biology


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