Nucleic Acids Research, 2003, Vol. 31, No. 15 4553-4560
© 2003 Oxford University Press
The computational analysis of scientific literature to define and recognize gene expression clusters
Department of Genetics and 1 Department of Biochemistry, Stanford University, Stanford, CA 94305, USA
*To whom correspondence should be addressed at 251 Campus Drive, MSOB X-215, Stanford University, Stanford, CA 94305-5479, USA. Tel: +1 650 725 3394; Fax: +1 650 725 7944; Email: russ.altman{at}stanford.edu
A limitation of many gene expression analytic approaches is that they do not incorporate comprehensive background knowledge about the genes into the analysis. We present a computational method that leverages the peer-reviewed literature in the automatic analysis of gene expression data sets. Including the literature in the analysis of gene expression data offers an opportunity to incorporate functional information about the genes when defining expression clusters. We have created a method that associates gene expression profiles with known biological functions. Our method has two steps. First, we apply hierarchical clustering to the given gene expression data set. Secondly, we use text from abstracts about genes to (i) resolve hierarchical cluster boundaries to optimize the functional coherence of the clusters and (ii) recognize those clusters that are most functionally coherent. In the case where a gene has not been investigated and therefore lacks primary literature, articles about well-studied homologous genes are added as references. We apply our method to two large gene expression data sets with different properties. The first contains measurements for a subset of well-studied Saccharomyces cerevisiae genes with multiple literature references, and the second contains newly discovered genes in Drosophila melanogaster; many have no literature references at all. In both cases, we are able to rapidly define and identify the biologically relevant gene expression profiles without manual intervention. In both cases, we identified novel clusters that were not noted by the original investigators.
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