Bioinformatics Advance Access originally published online on August 18, 2009
Bioinformatics 2009 25(21):2772-2779; doi:10.1093/bioinformatics/btp492
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The effects of probe binding affinity differences on gene expression measurements and how to deal with them
1 Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany, 2 Departments of Integrative Biology and Statistics, University of California, Berkeley, CA 94720, USA and 3 Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yue Yang Road, Shanghai, 200031, P.R. China
* To whom correspondence should be addressed.
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Abstract |
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Motivation: When comparing gene expression levels between species or strains using microarrays, sequence differences between the groups can cause false identification of expression differences. Our simulated dataset shows that a sequence divergence of only 1% between species can lead to falsely reported expression differences for >50% of the transcripts—similar levels of effect have been reported previously in comparisons of human and chimpanzee expression. We propose a method for identifying probes that cause such false readings, using only the microarray data, so that problematic probes can be excluded from analysis. We then test the power of the method to detect sequence differences and to correct for falsely reported expression differences. Our method can detect 70% of the probes with sequence differences using human and chimpanzee data, while removing only 18% of probes with no sequence differences. Although only 70% of the probes with sequence differences are detected, the effect of removing probes on falsely reported expression differences is more dramatic: the method can remove 98% of the falsely reported expression differences from a simulated dataset. We argue that the method should be used even when sequence data are available.
Contact: lachmann{at}eva.mpg.de
Supplementary information: Supplementary data are available at Bioinformatics online.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First authors.
Present address: Max Planck Institute for Evolutionary Biology, Ploen, Germany.
Associate Editor: Olga Troyanskaya
Received on April 9, 2009; revised on July 17, 2009; accepted on August 9, 2009
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