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Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification

A generic DNA microarray design applicable to any species would greatly benefit comparative genomics. We have addressed the feasibility of such a design by leveraging the great feature densities and relatively unbiased nature of genomic tiling microarrays. Specifically, we first divided each Homo sa...

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Detalles Bibliográficos
Autores principales: Royce, Thomas E., Rozowsky, Joel S., Gerstein, Mark B.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976448/
https://www.ncbi.nlm.nih.gov/pubmed/17686789
http://dx.doi.org/10.1093/nar/gkm549
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author Royce, Thomas E.
Rozowsky, Joel S.
Gerstein, Mark B.
author_facet Royce, Thomas E.
Rozowsky, Joel S.
Gerstein, Mark B.
author_sort Royce, Thomas E.
collection PubMed
description A generic DNA microarray design applicable to any species would greatly benefit comparative genomics. We have addressed the feasibility of such a design by leveraging the great feature densities and relatively unbiased nature of genomic tiling microarrays. Specifically, we first divided each Homo sapiens Refseq-derived gene's spliced nucleotide sequence into all of its possible contiguous 25 nt subsequences. For each of these 25 nt subsequences, we searched a recent human transcript mapping experiment's probe design for the 25 nt probe sequence having the fewest mismatches with the subsequence, but that did not match the subsequence exactly. Signal intensities measured with each gene's nearest-neighbor features were subsequently averaged to predict their gene expression levels in each of the experiment's thirty-three hybridizations. We examined the fidelity of this approach in terms of both sensitivity and specificity for detecting actively transcribed genes, for transcriptional consistency between exons of the same gene, and for reproducibility between tiling array designs. Taken together, our results provide proof-of-principle for probing nucleic acid targets with off-target, nearest-neighbor features.
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spelling pubmed-19764482007-09-26 Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification Royce, Thomas E. Rozowsky, Joel S. Gerstein, Mark B. Nucleic Acids Res Methods Online A generic DNA microarray design applicable to any species would greatly benefit comparative genomics. We have addressed the feasibility of such a design by leveraging the great feature densities and relatively unbiased nature of genomic tiling microarrays. Specifically, we first divided each Homo sapiens Refseq-derived gene's spliced nucleotide sequence into all of its possible contiguous 25 nt subsequences. For each of these 25 nt subsequences, we searched a recent human transcript mapping experiment's probe design for the 25 nt probe sequence having the fewest mismatches with the subsequence, but that did not match the subsequence exactly. Signal intensities measured with each gene's nearest-neighbor features were subsequently averaged to predict their gene expression levels in each of the experiment's thirty-three hybridizations. We examined the fidelity of this approach in terms of both sensitivity and specificity for detecting actively transcribed genes, for transcriptional consistency between exons of the same gene, and for reproducibility between tiling array designs. Taken together, our results provide proof-of-principle for probing nucleic acid targets with off-target, nearest-neighbor features. Oxford University Press 2007-08 2007-08-07 /pmc/articles/PMC1976448/ /pubmed/17686789 http://dx.doi.org/10.1093/nar/gkm549 Text en © 2007 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Methods Online
Royce, Thomas E.
Rozowsky, Joel S.
Gerstein, Mark B.
Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification
title Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification
title_full Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification
title_fullStr Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification
title_full_unstemmed Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification
title_short Toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification
title_sort toward a universal microarray: prediction of gene expression through nearest-neighbor probe sequence identification
topic Methods Online
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976448/
https://www.ncbi.nlm.nih.gov/pubmed/17686789
http://dx.doi.org/10.1093/nar/gkm549
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