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    Hybridization interactions between probesets in short oligo microarrays lead to spurious correlations.

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    Authors
    Okoniewski, Michal J
    Miller, Crispin J
    Affiliation
    Paterson Institute For Cancer Research, Christie Hospital site, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK. MOkoniewski@PICR.man.ac.uk
    Issue Date
    2006
    
    Metadata
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    Abstract
    BACKGROUND: Microarrays measure the binding of nucleotide sequences to a set of sequence specific probes. This information is combined with annotation specifying the relationship between probes and targets and used to make inferences about transcript- and, ultimately, gene expression. In some situations, a probe is capable of hybridizing to more than one transcript, in others, multiple probes can target a single sequence. These 'multiply targeted' probes can result in non-independence between measured expression levels. RESULTS: An analysis of these relationships for Affymetrix arrays considered both the extent and influence of exact matches between probe and transcript sequences. For the popular HGU133A array, approximately half of the probesets were found to interact in this way. Both real and simulated expression datasets were used to examine how these effects influenced the expression signal. It was found not only to lead to increased signal strength for the affected probesets, but the major effect is to significantly increase their correlation, even in situations when only a single probe from a probeset was involved. By building a network of probe-probeset-transcript relationships, it is possible to identify families of interacting probesets. More than 10% of the families contain members annotated to different genes or even different Unigene clusters. Within a family, a mixture of genuine biological and artefactual correlations can occur. CONCLUSION: Multiple targeting is not only prevalent, but also significant. The ability of probesets to hybridize to more than one gene product can lead to false positives when analysing gene expression. Comprehensive annotation describing multiple targeting is required when interpreting array data.
    Citation
    Hybridization interactions between probesets in short oligo microarrays lead to spurious correlations. 2006, 7:276 BMC Bioinformatics
    Journal
    BMC Bioinformatics
    URI
    http://hdl.handle.net/10541/72756
    DOI
    10.1186/1471-2105-7-276
    PubMed ID
    16749918
    Type
    Article
    Language
    en
    ISSN
    1471-2105
    ae974a485f413a2113503eed53cd6c53
    10.1186/1471-2105-7-276
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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