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Impact of the spotted microarray preprocessing method on fold-change compression and variance stability.

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Ambroise, Jérôme [FUCAM] Bearzatto, Bertrand [UCL] Robert, Annie [UCL] Govaerts, Bernadette [UCL] Macq, Benoît [UCL] Gala, Jean-Luc [UCL]

ABSTRACT: BACKGROUND: The standard approach for preprocessing spotted microarray data is to subtract the local background intensity from the spot foreground intensity, to perform a log2 transformation and to normalise the data with a global median or a loess normalisation. Although well motivated, standard approaches for background correction and for transformation have been widely criticised because they produce high variance at low intensities. Whereas various alternatives to the standard background correction methods and to log2 transformation were proposed, impacts of both successive processing steps were not compared in an objective way. RESULTS: In this study, we assessed the impact of eight preprocessing methods combining four background correction and two transformations methods (the log2 and the glog), by using data from the MAQC study. The current results indicate that most preprocessing methods produce fold-change compression at low intensities. Fold-change compression was minimised using the Standard and the Edwards background correction methods coupled with a log2 transformation. The drawback of both methods is a high variance at low intensities which consequently produced poor estimations of the p-values. On the other hand, effective stabilisation of the variance as well as better estimations of the p-values were observed after the glog transformation. CONCLUSION: As both fold-change magnitudes and p-values are important in the context of microarray class comparison studies, we therefore recommend to combine the Edwards correction with a hybrid transformation method that uses the log2 transformation to estimate fold-change magnitudes and the glog transformation to estimate p-values.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2011
Language Anglais
Journal information "BMC Bioinformatics" - Vol. 12, p. 413 (2011)
Peer reviewed yes
Publisher BioMed Central Ltd. ((United Kingdom) [S.l.])
issn 1471-2105
e-issn 1471-2105
Publication status Publié
Affiliations UCL - SSH/LIDAM/ISBA - Institut de Statistique, Biostatistique et Sciences Actuarielles
UCL - SST/ICTM/ELEN - Pôle en ingénierie électrique
UCL - SSS/IREC/CTMA - Centre de technologies moléculaires appliquées (plate-forme technologique)
UCL - SSS/IREC/EPID - Pôle d'épidémiologie et biostatistique
UCL - (SLuc) Département de médecine interne et services associés
UCL - (SLuc) Service de pneumologie
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Bibliographic reference Ambroise, Jérôme ; Bearzatto, Bertrand ; Robert, Annie ; Govaerts, Bernadette ; Macq, Benoît ; et. al. Impact of the spotted microarray preprocessing method on fold-change compression and variance stability.. In: BMC Bioinformatics, Vol. 12, p. 413 (2011)
Permanent URL http://hdl.handle.net/2078.1/91495