From Gene Networks to Gene Function

  1. Thomas Schlitt1,3,
  2. Kimmo Palin2,
  3. Johan Rung1,
  4. Sabine Dietmann1,
  5. Michael Lappe1,
  6. Esko Ukkonen2, and
  7. Alvis Brazma1
  1. 1 European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
  2. 2 Department of Computer Science, FIN-00014 University of Helsinki, Finland

Abstract

We propose a novel method to identify functionally related genes based on comparisons of neighborhoods in gene networks. This method does not rely on gene sequence or protein structure homologies, and it can be applied to any organism and a wide variety of experimental data sets. The character of the predicted gene relationships depends on the underlying networks;they concern biological processes rather than the molecular function. We used the method to analyze gene networks derived from genome-wide chromatin immunoprecipitation experiments, a large-scale gene deletion study, and from the genomic positions of consensus binding sites for transcription factors of the yeast Saccharomyces cerevisiae. We identified 816 functional relationships between 159 genes and show that these relationships correspond to protein–protein interactions, co-occurrence in the same protein complexes, and/or co-occurrence in abstracts of scientific articles. Our results suggest functions for seven previously uncharacterized yeast genes: KIN3 and YMR269W may be involved in biological processes related to cell growth and/or maintenance, whereas IES6, YEL008W, YEL033W, YHL029C, YMR010W, and YMR031W-A are likely to have metabolic functions.

Footnotes

  • [Supplemental material is available online at www.genome.org.]

  • 4 The SGD database has been recently updated and the KIN3 gene is now assigned to the biological process “chromosome segregation” based on an experimental analysis performed by Chen et al. 2002. This annotation is corresponding well with our functional prediction. “Chromosome segregation” is a child process of “DNA replication andchromosome cycle,” which itself is a child process of “cell cycle” according to SGD and GO.

  • Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.1111403.

  • 3 Corresponding author. E-MAIL schlitt{at}ebi.ac.uk; FAX 44-1223-494468.

    • Accepted September 24, 2003.
    • Received December 18, 2002.
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