TY - JOUR
T1 - Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification
AU - Yanai, Itai
AU - Benjamin, Hila
AU - Shmoish, Michael
AU - Chalifa-Caspi, Vered
AU - Shklar, Maxim
AU - Ophir, Ron
AU - Bar-Even, Arren
AU - Horn-Saban, Shirley
AU - Safran, Marilyn
AU - Domany, Eytan
AU - Lancet, Doron
AU - Shmueli, Orit
N1 - Funding Information:
I.Y. is a Koshland Scholar, D.L. is the incumbent of the Ralph and Lois Silver Chair in Human Genomics, and E.D. is the incumbent of the Henry J. Leir Professorial Chair. This work was made possible by the generosity of the Abraham and Judith Goldwasser Foundation. It was further supported by the Crown Human Genome Center and by the Koshland Center for Basic Research.
PY - 2005/3/1
Y1 - 2005/3/1
N2 - 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: To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index τ, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15 < τ < 0.85 were found to constitute >50% of all expression patterns. We developed a binary classification, indicating for every gene the lB tissues in which it is overly expressed, and the 12 - lB tissues in which it shows low expression. The 85 dominant midrange patterns with lB = 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.
AB - 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: To obtain such novel information genome-wide, we have determined the mRNA expression levels for one of the largest hitherto analyzed set of 62839 probesets in 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index τ, valued between 0 for housekeeping genes and 1 for tissue-specific genes, genes with midrange profiles having 0.15 < τ < 0.85 were found to constitute >50% of all expression patterns. We developed a binary classification, indicating for every gene the lB tissues in which it is overly expressed, and the 12 - lB tissues in which it shows low expression. The 85 dominant midrange patterns with lB = 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.
UR - http://www.scopus.com/inward/record.url?scp=20144376345&partnerID=8YFLogxK
U2 - 10.1093/bioinformatics/bti042
DO - 10.1093/bioinformatics/bti042
M3 - Article
C2 - 15388519
AN - SCOPUS:20144376345
SN - 1367-4803
VL - 21
SP - 650
EP - 659
JO - Bioinformatics
JF - Bioinformatics
IS - 5
ER -