Research ExplorerPublicationsThe choice of the filtering method in microarrays affects th...

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

Standard

The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome. / Castagné, Raphaële; Rotival, Maxime; Zeller, Tanja; Wild, Philipp S; Truong, Vinh; Trégouët, David-Alexandre; Munzel, Thomas; Ziegler, Andreas; Cambien, François; Blankenberg, Stefan; Tiret, Laurence.

In: PLOS ONE, Vol. 6, No. 9, 2011, p. e23956.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Castagné, R, Rotival, M, Zeller, T, Wild, PS, Truong, V, Trégouët, D-A, Munzel, T, Ziegler, A, Cambien, F, Blankenberg, S & Tiret, L 2011, 'The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome', PLOS ONE, vol. 6, no. 9, pp. e23956. https://doi.org/10.1371/journal.pone.0023956

APA

Castagné, R., Rotival, M., Zeller, T., Wild, P. S., Truong, V., Trégouët, D-A., Munzel, T., Ziegler, A., Cambien, F., Blankenberg, S., & Tiret, L. (2011). The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome. PLOS ONE, 6(9), e23956. https://doi.org/10.1371/journal.pone.0023956

Vancouver

Castagné R, Rotival M, Zeller T, Wild PS, Truong V, Trégouët D-A et al. The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome. PLOS ONE. 2011;6(9):e23956. https://doi.org/10.1371/journal.pone.0023956

Bibtex

@article{666034a4b68748b3a44a363eb6aa1945,
title = "The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome",
abstract = "BACKGROUND: 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.METHODOLOGY/PRINCIPAL FINDINGS: 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.CONCLUSION/SIGNIFICANCE: 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.",
keywords = "Animals, Chromosomes, Human, X/genetics, Dosage Compensation, Genetic/genetics, Female, Gene Expression Profiling, Genes, X-Linked/genetics, Genomic Imprinting, HEK293 Cells, Humans, Male, Mice, Models, Genetic, Monocytes/metabolism, Oligonucleotide Array Sequence Analysis/methods, RNA, Messenger/genetics",
author = "Rapha{\"e}le Castagn{\'e} and Maxime Rotival and Tanja Zeller and Wild, {Philipp S} and Vinh Truong and David-Alexandre Tr{\'e}gou{\"e}t and Thomas Munzel and Andreas Ziegler and Fran{\c c}ois Cambien and Stefan Blankenberg and Laurence Tiret",
year = "2011",
doi = "10.1371/journal.pone.0023956",
language = "English",
volume = "6",
pages = "e23956",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

RIS

TY - JOUR

T1 - The choice of the filtering method in microarrays affects the inference regarding dosage compensation of the active X-chromosome

AU - Castagné, Raphaële

AU - Rotival, Maxime

AU - Zeller, Tanja

AU - Wild, Philipp S

AU - Truong, Vinh

AU - Trégouët, David-Alexandre

AU - Munzel, Thomas

AU - Ziegler, Andreas

AU - Cambien, François

AU - Blankenberg, Stefan

AU - Tiret, Laurence

PY - 2011

Y1 - 2011

N2 - BACKGROUND: 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.METHODOLOGY/PRINCIPAL FINDINGS: 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.CONCLUSION/SIGNIFICANCE: 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.

AB - BACKGROUND: 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.METHODOLOGY/PRINCIPAL FINDINGS: 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.CONCLUSION/SIGNIFICANCE: 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.

KW - Animals

KW - Chromosomes, Human, X/genetics

KW - Dosage Compensation, Genetic/genetics

KW - Female

KW - Gene Expression Profiling

KW - Genes, X-Linked/genetics

KW - Genomic Imprinting

KW - HEK293 Cells

KW - Humans

KW - Male

KW - Mice

KW - Models, Genetic

KW - Monocytes/metabolism

KW - Oligonucleotide Array Sequence Analysis/methods

KW - RNA, Messenger/genetics

U2 - 10.1371/journal.pone.0023956

DO - 10.1371/journal.pone.0023956

M3 - SCORING: Journal article

C2 - 21912656

VL - 6

SP - e23956

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 9

ER -