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Nucleic Acids Research 2005 33(11):e100; doi:10.1093/nar/gni095
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Published online 24 June 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions{at}oupjournals.org

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Enhanced microarray performance using low complexity representations of the transcriptome

Gaëlle Rondeau, Michael McClelland, Toan Nguyen, Rosana Risques1, Yipeng Wang, Martin Judex2, Ann H. Cho and John Welsh*

Sidney Kimmel Cancer Center 10835 Altman Row, San Diego, CA 92121, USA 1Department of Pathology, University of Washington Box 357705, 1959 NE Pacific Ave HSB K-081, Seattle, WA 98195, USA 2Klinikum rechts der Isar III. Medizinische Klinik, Ismaningerstrasse 22, 81675 München, Germany

*To whom correspondence should be addressed. Tel: +1 858 450 5990; Fax: +1 858 450 3251; Email: jwelsh{at}skcc.org

Received February 16, 2005. Revised May 10, 2005. Accepted May 29, 2005.

Low abundance mRNAs are more difficult to examine using microarrays than high abundance mRNAs due to the effect of concentration on hybridization kinetics and signal-to-noise ratios. This report describes the use of low complexity representations (LCRs) of mRNA as the targets for cDNA microarrays. Individual sequences in LCRs are more highly represented than in the mRNA populations from which they are derived, leading to favorable hybridization kinetics. LCR targets permit the measurement of abundance changes that are difficult to measure using oligo(dT) priming for target synthesis. An oligo(dT)-primed target and three LCRs detect twice as many differentially regulated genes as could be detected by the oligo(dT)-primed target alone, in an experiment in which serum-starved fibroblasts responded to the reintroduction of serum. Thus, this target preparation strategy considerably increases the sensitivity of cDNA microarrays.


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