An Approach for Clustering Gene Expression Data with Error Information

BMC Bioinformatics 7:17, 2006

Brian Tjaden



Background:   Clustering of gene expression patterns is a well-studied technique for elucidating trends across large numbers of transcripts and for identifying likely co-regulated genes. Even the best clustering methods, however, are unlikely to provide meaningful results if too much of the data is unreliable. With the maturation of microarray technology, a wealth of research on statistical analysis of gene expression data has encouraged researchers to consider error and uncertainty in their microarray experiments, so that experiments are being performed increasingly with repeat spots per gene per chip and with repeat experiments. One of the challenges is to incorporate the measurement error information into downstream analyses of gene expression data, such as traditional clustering techniques.
Results:   In this study, a clustering approach is presented which incorporates both gene expression values and error information about the expression measurements. Using repeat expression measurements, the error of each gene expression measurement in each experiment condition is estimated, and this measurement error information is incorporated directly into the clustering algorithm. The algorithm, CORE (Clustering Of Repeat Expression data), is presented and its performance is validated using statistical measures. By using error information about gene expression measurements, the clustering approach is less sensitive to noise in the underlying data and it is able to achieve more accurate clusterings. Results are described for both synthetic expression data as well as real gene expression data from Escherichia coli and Saccharomyces cerevisiae.
Conclusions:   The additional information provided by replicate gene expression measurements is a valuable asset in effective clustering. Gene expression profiles with high errors, as determined from repeat measurements, may be unreliable and may associate with different clusters, whereas gene expression profiles with low errors can be clustered with higher specificity. Results indicate that including error information from repeat gene expression measurements can lead to significant improvements in clustering accuracy.

Escherichia coli Gene Expression Data

  • Gene expression data for 4248 E. coli genes across 55 experiments.
    Expression values and error information are calculated from raw
    data using the approach of Li and Wong (2001).
Text (tab delimited)    Excel
  • The comlete raw expression data is available from the follow sources:
Selinger et al. 2000
Masuda et al. 2002
Tjaden et al. 2002
Selinger et al. 2003

Saccharomyces cerevisiae Gene Expression Data

  • Gene expression data for 205 yeast genes across 20 experiments:
Text (tab delimited)    Excel
  • The complete raw expression data is available from the follow source:
Ideker et al. 2001