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Bioinformatics Advance Access first published online on September 23, 2004
This version published online on September 30, 2004
Bioinformatics, doi:10.1093/bioinformatics/bti042
Bioinformatics © Oxford University Press 2004; all rights reserved
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Received April 14, 2004
Revised June 14, 2004
Accepted September 19, 2004

Article

Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification

Itai Yanai 1, Hila Benjamin 2, Michael Shmoish 1, Vered Chalifa-Caspi 3, Maxim Shklar 1, Ron Ophir 3, Arren Bar-Even 1, Shirley Horn-Saban 3, Marilyn Safran 3, Eytan Domany 4, Doron Lancet 1*, and Orit Shmueli 1

1 Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel
2 Department of Molecular Genetics, Weizmann Institute of Science, 76100 Rehovot, Israel; Department of Physics of Complex Systems, Weizmann Institute of Science, 76100 Rehovot, Israel
3 Department of Biological Services, Weizmann Institute of Science, 76100 Rehovot, Israel
4 Department of Physics of Complex Systems, Weizmann Institute of Science, 76100 Rehovot, Israel

* To whom correspondence should be addressed. E-mail: doron.lancet{at}weizmann.ac.il.


  Abstract

Motivation: Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression.

Results: In order to obtain such novel information genome-wide, we have determined the mRNA expression levels for the one of the largest hitherto analyzed set of 62,839 probesets in 12 representative normal human tissues. Indeed, when using a newly-defined graded tissue specificity index {tau}, valued between 0 for housekeeping genes and 1 for tissue specific genes, genes with midrange profiles having 0.15 < {tau} < 0.85 were found to constitute >50% of all expression patterns. We developed a binary classification, indicating for every gene the IB tissues in which it is overly expressed, and the 12 - IB tissues in which it shows low expression. The 85 dominant midrange patterns with IB = 2 to 11 were found to be bimodally distributed, and to contribute most significantly to the definition of tissue specification dendrograms. Our analyses provide a novel route to infer expression profiles for presumed ancestral nodes in the tissue dendrogram. Such definition has uncovered an unsuspected correlation, whereby de novo enhancement and diminution of gene expression go hand in hand. These findings highlight the importance of gene suppression events, with implications to the course of tissue specification in ontogeny and phylogeny.

Availability: All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803.

Supplementary Information: Four tables.


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