The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.

<h4>Background</h4>The hypothesis of dosage compensation of genes of the X chromosome, supported by previous microarray studies, was recently challenged by RNA-sequencing data. It was suggested that microarray studies were biased toward an over-estimation of X-linked expression levels as...

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Autores principales: Raphaële Castagné, Maxime Rotival, Tanja Zeller, Philipp S Wild, Vinh Truong, David-Alexandre Trégouët, Thomas Munzel, Andreas Ziegler, François Cambien, Stefan Blankenberg, Laurence Tiret
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spelling oai:doaj.org-article:6a762a91bfd44c10886c9c5730c7ffe82021-11-18T06:46:47ZThe choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.1932-620310.1371/journal.pone.0023956https://doaj.org/article/6a762a91bfd44c10886c9c5730c7ffe82011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21912656/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The hypothesis of dosage compensation of genes of the X chromosome, supported by previous microarray studies, was recently challenged by RNA-sequencing data. It was suggested that microarray studies were biased toward an over-estimation of X-linked expression levels as a consequence of the filtering of genes below the detection threshold of microarrays.<h4>Methodology/principal findings</h4>To investigate this hypothesis, we used microarray expression data from circulating monocytes in 1,467 individuals. In total, 25,349 and 1,156 probes were unambiguously assigned to autosomes and the X chromosome, respectively. Globally, there was a clear shift of X-linked expressions toward lower levels than autosomes. We compared the ratio of expression levels of X-linked to autosomal transcripts (X∶AA) using two different filtering methods: 1. gene expressions were filtered out using a detection threshold irrespective of gene chromosomal location (the standard method in microarrays); 2. equal proportions of genes were filtered out separately on the X and on autosomes. For a wide range of filtering proportions, the X∶AA ratio estimated with the first method was not significantly different from 1, the value expected if dosage compensation was achieved, whereas it was significantly lower than 1 with the second method, leading to the rejection of the hypothesis of dosage compensation. We further showed in simulated data that the choice of the most appropriate method was dependent on biological assumptions regarding the proportion of actively expressed genes on the X chromosome comparative to the autosomes and the extent of dosage compensation.<h4>Conclusion/significance</h4>This study shows that the method used for filtering out lowly expressed genes in microarrays may have a major impact according to the hypothesis investigated. The hypothesis of dosage compensation of X-linked genes cannot be firmly accepted or rejected using microarray-based data.Raphaële CastagnéMaxime RotivalTanja ZellerPhilipp S WildVinh TruongDavid-Alexandre TrégouëtThomas MunzelAndreas ZieglerFrançois CambienStefan BlankenbergLaurence TiretPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e23956 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Raphaële Castagné
Maxime Rotival
Tanja Zeller
Philipp S Wild
Vinh Truong
David-Alexandre Trégouët
Thomas Munzel
Andreas Ziegler
François Cambien
Stefan Blankenberg
Laurence Tiret
The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.
description <h4>Background</h4>The hypothesis of dosage compensation of genes of the X chromosome, supported by previous microarray studies, was recently challenged by RNA-sequencing data. It was suggested that microarray studies were biased toward an over-estimation of X-linked expression levels as a consequence of the filtering of genes below the detection threshold of microarrays.<h4>Methodology/principal findings</h4>To investigate this hypothesis, we used microarray expression data from circulating monocytes in 1,467 individuals. In total, 25,349 and 1,156 probes were unambiguously assigned to autosomes and the X chromosome, respectively. Globally, there was a clear shift of X-linked expressions toward lower levels than autosomes. We compared the ratio of expression levels of X-linked to autosomal transcripts (X∶AA) using two different filtering methods: 1. gene expressions were filtered out using a detection threshold irrespective of gene chromosomal location (the standard method in microarrays); 2. equal proportions of genes were filtered out separately on the X and on autosomes. For a wide range of filtering proportions, the X∶AA ratio estimated with the first method was not significantly different from 1, the value expected if dosage compensation was achieved, whereas it was significantly lower than 1 with the second method, leading to the rejection of the hypothesis of dosage compensation. We further showed in simulated data that the choice of the most appropriate method was dependent on biological assumptions regarding the proportion of actively expressed genes on the X chromosome comparative to the autosomes and the extent of dosage compensation.<h4>Conclusion/significance</h4>This study shows that the method used for filtering out lowly expressed genes in microarrays may have a major impact according to the hypothesis investigated. The hypothesis of dosage compensation of X-linked genes cannot be firmly accepted or rejected using microarray-based data.
format article
author Raphaële Castagné
Maxime Rotival
Tanja Zeller
Philipp S Wild
Vinh Truong
David-Alexandre Trégouët
Thomas Munzel
Andreas Ziegler
François Cambien
Stefan Blankenberg
Laurence Tiret
author_facet Raphaële Castagné
Maxime Rotival
Tanja Zeller
Philipp S Wild
Vinh Truong
David-Alexandre Trégouët
Thomas Munzel
Andreas Ziegler
François Cambien
Stefan Blankenberg
Laurence Tiret
author_sort Raphaële Castagné
title The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.
title_short The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.
title_full The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.
title_fullStr The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.
title_full_unstemmed The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome.
title_sort choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active x-chromosome.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/6a762a91bfd44c10886c9c5730c7ffe8
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