Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification.
BACKGROUND
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
To obtain such novel information genome-wide, we have determined the mRNA expression levels for 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 I(B) tissues in which it is overly expressed, and the 12-I(B) tissues in which it shows low expression. The 85 dominant midrange patterns with I(B)=2-11 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.


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


BACKGROUND
doron.lancet@weizmann.ac.il


BACKGROUND
Four tables available at the above site.
Yanai
Itai
I
Department of Molecular Genetics, Weizmann Institute of Science 76100 Rehovot, Israel.
Benjamin
Hila
H
Shmoish
Michael
M
Chalifa-Caspi
Vered
V
Shklar
Maxim
M
Ophir
Ron
R
Bar-Even
Arren
A
Horn-Saban
Shirley
S
Safran
Marilyn
M
Domany
Eytan
E
Lancet
Doron
D
Shmueli
Orit
O
D000465:Algorithms; D002874:Chromosome Mapping / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D009928:Organ Specificity; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012984:Software; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D020543:Proteome; D014157:Transcription Factors