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Physically grounded approach for estimating gene expression from microarray data.


ABSTRACT: High-throughput technologies, including gene-expression microarrays, hold great promise for the systems-level study of biological processes. Yet, challenges remain in comparing microarray data from different sources and extracting information about low-abundance transcripts. We demonstrate that these difficulties arise from limitations in the modeling of the data. We propose a physically motivated approach for estimating gene-expression levels from microarray data, an approach neglected in the microarray literature. We separately model the noises specific to sample amplification, hybridization, and fluorescence detection, combining these into a parsimonious description of the variability sources in a microarray experiment. We find that our model produces estimates of gene expression that are reproducible and unbiased. While the details of our model are specific to gene-expression microarrays, we argue that the physically grounded modeling approach we pursue is broadly applicable to other molecular biology technologies.

SUBMITTER: McMullen PD 

PROVIDER: S-EPMC2922271 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Physically grounded approach for estimating gene expression from microarray data.

McMullen Patrick D PD   Morimoto Richard I RI   Amaral Luís A Nunes LA  

Proceedings of the National Academy of Sciences of the United States of America 20100719 31


High-throughput technologies, including gene-expression microarrays, hold great promise for the systems-level study of biological processes. Yet, challenges remain in comparing microarray data from different sources and extracting information about low-abundance transcripts. We demonstrate that these difficulties arise from limitations in the modeling of the data. We propose a physically motivated approach for estimating gene-expression levels from microarray data, an approach neglected in the m  ...[more]

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