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Research Article

Local graph alignment and motif search in biological networks

Johannes Berg and Michael Lässig

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    PNAS October 12, 2004 101 (41) 14689-14694; https://doi.org/10.1073/pnas.0305199101
    1. Edited by Richard M. Karp, International Computer Science Institute, Berkeley, CA, and approved July 8, 2004 (received for review August 13, 2003)

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    Abstract

    Interaction networks are of central importance in postgenomic molecular biology, with increasing amounts of data becoming available by high-throughput methods. Examples are gene regulatory networks or protein interaction maps. The main challenge in the analysis of these data is to read off biological functions from the topology of the network. Topological motifs, i.e., patterns occurring repeatedly at different positions in the network, have recently been identified as basic modules of molecular information processing. In this article, we discuss motifs derived from families of mutually similar but not necessarily identical patterns. We establish a statistical model for the occurrence of such motifs, from which we derive a scoring function for their statistical significance. Based on this scoring function, we develop a search algorithm for topological motifs called graph alignment, a procedure with some analogies to sequence alignment. The algorithm is applied to the gene regulation network of Escherichia coli.

    Footnotes

    • ↵ † To whom correspondence should be addressed. E-mail: berg@thp.uni-koeln.de.

    • This paper was submitted directly (Track II) to the PNAS office.

    • Copyright © 2004, The National Academy of Sciences
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    Proceedings of the National Academy of Sciences of the United States of America: 101 (41)
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    • Article
      • Abstract
      • Graphs and Patterns
      • Graph Alignments and Motifs
      • Statistics of Individual Subgraphs
      • Statistics in the Presence of a Template
      • Statistics of Correlated Subgraphs
      • The Scoring Function
      • Maximum Score Alignments and Parametric Optimization
      • Results and Discussion
      • Acknowledgments
      • Footnotes
      • References
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