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Using networks to measure similarity between genes: association index selection


A Corrigendum to this article was published on 27 February 2014

This article has been updated


Biological networks can be used to functionally annotate genes on the basis of interaction-profile similarities. Metrics known as association indices can be used to quantify interaction-profile similarity. We provide an overview of commonly used association indices, including the Jaccard index and the Pearson correlation coefficient, and compare their performance in different types of analyses of biological networks. We introduce the Guide for Association Index for Networks (GAIN), a web tool for calculating and comparing interaction-profile similarities and defining modules of genes with similar profiles.

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Figure 1: Measuring interaction-profile similarity between two nodes using association indices.
Figure 2: GAIN web tool for the calculation and clustering of association indices.
Figure 3: Using association indices to identify modules in a gene-to-phenotype network.
Figure 4: Comparing association indices in the C. elegans gene-to-phenotype network.
Figure 5: Predicting gene function.
Figure 6: Application of association indices to network integration.

Change history

  • 27 January 2014

    In the version of this article initially published, the formula describing the connection specificity index (CSI) in Box 2 was incorrect. The denominator in the fraction of the CSI equation originally read "ny"; the correct denominator is "# of X-type nodes in the network." The error has been corrected in the HTML and PDF versions of the article.


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We thank members of A.J.M.W.'s lab, R. McCord and B. Lajoie for discussions and critical reading of the manuscript. We thank J.C. Bare (Institute of Systems Biology) for helpful advice in the development of GAIN. This work was supported by the US National Institutes of Health grants DK068429 and GM082971 to A.J.M.W. J.I.F.B. is partially supported by a postdoctoral fellowship from the Pew Latin American Fellows Program. J.N. and C.L.M. are partially supported by grant DBI-0953881 from the US National Science Foundation.

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J.I.F.B. and A.J.M.W. conceived the project; J.I.F.B. performed the data analysis with the assistance of A.D., J.N. and C.L.M.; A.D. and J.I.F.B. developed the GAIN web tool in collaboration with J.N., C.L.M. and J.M.S.; J.I.F.B. and A.J.M.W. wrote the paper.

Corresponding authors

Correspondence to Juan I Fuxman Bass or Albertha J M Walhout.

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The authors declare no competing financial interests.

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Supplementary Figures 1–3, Supplementary Table 1 and Supplementary Methods (PDF 948 kb)

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Bass, J., Diallo, A., Nelson, J. et al. Using networks to measure similarity between genes: association index selection. Nat Methods 10, 1169–1176 (2013).

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