Unknown,Transcriptomics,Genomics,Proteomics

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Genome-Scale Identification of Membrane-Associated Human mRNAs

ABSTRACT: The subcellular localization of proteins is critical to their biological roles. Moreover, whether a protein is membrane-bound, secreted, or intracellular affects the usefulness of, and the strategies for, using a protein as a diagnostic marker or a target for therapy. We employed a rapid and efficient experimental approach to classify thousands of human gene products as either membrane-associated/secreted (MS) or cytosolic/nuclear (CN). Using subcellular fractionation methods, we separated mRNAs associated with membranes from those associated with the soluble cytosolic fraction and analyzed these two pools by comparative hybridization to DNA microarrays. Analysis of 11 different human cell lines, representing lymphoid, myeloid, breast, ovarian, hepatic, colon, and prostate tissues, identified more than 5,000 previously uncharacterized MS and more than 6,400 putative CN genes at high confidence levels. The experimentally determined localizations correlated well with in silico predictions of signal peptides and transmembrane domains, but also significantly increased the number of human genes that could be cataloged as encoding either MS or CN proteins. Using gene expression data from a variety of primary human malignancies and normal tissues, we rationally identified hundreds of MS gene products that are significantly overexpressed in tumors compared to normal tissues and thus represent candidates for serum diagnostic tests or monoclonal antibody-based therapies. Finally, we used the catalog of CN gene products to generate sets of candidate markers of organ-specific tissue injury. The large-scale annotation of subcellular localization reported here will serve as a reference database and will aid in the rational design of diagnostic tests and molecular therapies for diverse diseases. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Using regression correlation

ORGANISM(S): Homo sapiens

SUBMITTER: Max Diehn

PROVIDER: E-GEOD-4175 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-scale identification of membrane-associated human mRNAs.

Diehn Maximilian M Bhattacharya Ramona R Botstein David D Brown Patrick O PO

PLoS genetics 20060113 1

The subcellular localization of proteins is critical to their biological roles. Moreover, whether a protein is membrane-bound, secreted, or intracellular affects the usefulness of, and the strategies for, using a protein as a diagnostic marker or a target for therapy. We employed a rapid and efficient experimental approach to classify thousands of human gene products as either "membrane-associated/secreted" (MS) or "cytosolic/nuclear" (CN). Using subcellular fractionation methods, we separated m ...[more]

PMID: 16415983

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Dataset Information

Genome-Scale Identification of Membrane-Associated Human mRNAs

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Genome-scale identification of membrane-associated human mRNAs.

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