A gene recommender algorithm to identify coexpressed genes in C. elegans - PubMed (original) (raw)

A gene recommender algorithm to identify coexpressed genes in C. elegans

Art B Owen et al. Genome Res. 2003 Aug.

Abstract

One of the most important uses of whole-genome expression data is for the discovery of new genes with similar function to a given list of genes (the query) already known to have closely related function. We have developed an algorithm, called the gene recommender, that ranks genes according to how strongly they correlate with a set of query genes in those experiments for which the query genes are most strongly coregulated. We used the gene recommender to find other genes coexpressed with several sets of query genes, including genes known to function in the retinoblastoma complex. Genetic experiments confirmed that one gene (JC8.6) identified by the gene recommender acts with lin-35 Rb to regulate vulval cell fates, and that another gene (wrm-1) acts antagonistically. We find that the gene recommender returns lists of genes with better precision, for fixed levels of recall, than lists generated using the C. elegans expression topomap.

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Figures

Figure 1

Figure 1

Some DNA microarray experiments show coregulation of the genes in the Rb query. Histogram of experiment scores obtained using the retinoblastoma query (black bars) or using 100 random queries of the same size (white bars). The arrow indicates the maximum experiment score obtained across all the randomizations. A substantial fraction of the experiment Z scores obtained using the retinoblastoma query were higher than the maximum Z score obtained from random queries.

Figure 2

Figure 2

Leave-one-out cross-validation. Histograms of percentile ranks obtained after removing a gene from a query list of genes, building a cassette around the remaining query genes, and then scoring the held-out gene. Open bars show the histogram obtained from random queries ranging in size from 4 to 50; black bars show the histogram obtained from all the queries used in this study. The inset is an expanded view of the highest-scoring genes.

Figure 3

Figure 3

Expression profiles of genes in the Rb hit list. The germ line experiments compared expression in wild-type animals to glp-4 mutants lacking a germ line, and in mutants making only sperm to mutants making only oocytes (Reinke et al. 2000). The development experiments compared expression in whole wild-type worms throughout development and in hermaphrodites versus males (Jiang et al. 2001). The dauer experiments compared expression as animals exit the dauer stage following feeding in a timecourse experiment (Wang and Kim 2003). Rb query genes are shown in red. Scale shows level of expression.

Figure 4

Figure 4

JC8.6(RNAi) results in a Muv phenotype similar to lin-35 Rb(RNAi). (A) JC8.6(RNAi), (B) JC8.6(RNAi) lin-8(n111), (C) JC8.6(RNAi) lin-9(n112), (D) lin-35 Rb(RNAi) lin-8(n111). Arrows point to the vulva in A and C, and to pseudovulvae in B and D. Adults were fed bacteria expressing JC8.6 dsRNA, and the phenotypes of their progeny were scored. Scale bar is 20 μM.

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References

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WEB SITE REFERENCES

    1. http://pmgm2.stanford.edu/~kimlab/cassettes; details of the gene recommender and a Web interface to our software and data.
    1. http://www-stat.stanford.edu/~owen/transposable; articles and links comparing data analysis of DNA expression, recommender engines, search engines, and educational testing.

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