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

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 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. AVAILABILITY All data and analyses are publically available at the GeneNote website, http://genecards.weizmann.ac.il/genenote/ and, GEO accession GSE803. CONTACT doron.lancet@weizmann.ac.il SUPPLEMENTARY INFORMATION Four tables available at the above site.

[1]  Wei-Min Liu,et al.  Robust estimators for expression analysis , 2002, Bioinform..

[2]  Michael Rosenfeld,et al.  Signaling and transcriptional control of pituitary development. , 2002, Current opinion in genetics & development.

[3]  G. Getz,et al.  Coupled two-way clustering analysis of gene microarray data. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Marc S Halfon,et al.  Exploring genetic regulatory networks in metazoan development: methods and models. , 2002, Physiological genomics.

[5]  A Orimo,et al.  Molecular cloning of ring finger protein 21 (RNF21)/interferon-responsive finger protein (ifp1), which possesses two RING-B box-coiled coil domains in tandem. , 2000, Genomics.

[6]  Yangrae Cho,et al.  Gene-expression profile comparisons distinguish seven organs of maize , 2002, Genome Biology.

[7]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[8]  H. Cerutti,et al.  RNA interference: traveling in the cell and gaining functions? , 2003, Trends in genetics : TIG.

[9]  Doron Lancet,et al.  GeneTide - Terra Incognita Discovery Endeavor mining ESTs and expression data to elucidate known and de-novo GeneCards/spl reg/ genes , 2004 .

[10]  Daniel St Johnston,et al.  The art and design of genetic screens: Drosophila melanogaster , 2002, Nature Reviews Genetics.

[11]  Doron Lancet,et al.  GeneNote: whole genome expression profiles in normal human tissues. , 2003, Comptes rendus biologies.

[12]  M. Watson,et al.  Expression , 2019, The Oxford Handbook of Western Music and Philosophy.

[13]  Kimberly Walter,et al.  Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. , 2002, The American journal of pathology.

[14]  A. Orth,et al.  Large-scale analysis of the human and mouse transcriptomes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  G. Stephanopoulos,et al.  A compendium of gene expression in normal human tissues. , 2001, Physiological genomics.

[16]  I. Yanai,et al.  Incongruent expression profiles between human and mouse orthologous genes suggest widespread neutral evolution of transcription control. , 2004, Omics : a journal of integrative biology.

[17]  Gideon Rechavi,et al.  DNA microarray analysis of genes involved in p53 mediated apoptosis: activation of Apaf-1 , 2001, Oncogene.

[18]  E. Levanon,et al.  Human housekeeping genes are compact. , 2003, Trends in genetics : TIG.

[19]  Martin J. Lercher,et al.  Clustering of housekeeping genes provides a unified model of gene order in the human genome , 2002, Nature Genetics.

[20]  S. Pääbo,et al.  A Neutral Model of Transcriptome Evolution , 2004, PLoS biology.

[21]  Doron Lancet,et al.  GeneAnnot: Interfacing GeneCards with high-throughput gene expression compendia , 2003, Briefings Bioinform..

[22]  Doron Lancet,et al.  GeneLoc: exon-based integration of human genome maps , 2003, ISMB.

[23]  Tsviya Olender,et al.  GeneCardsTM 2002: towards a complete, object-oriented, human gene compendium , 2002, Bioinform..

[24]  Rafael A Irizarry,et al.  Exploration, normalization, and summaries of high density oligonucleotide array probe level data. , 2003, Biostatistics.

[25]  Tsippi Iny Stein,et al.  GeneAnnot: comprehensive two-way linking between oligonucleotide array probesets and GeneCards genes. , 2004, Bioinformatics.

[26]  Doron Lancet,et al.  GeneTide - Terra Incognita Discovery Endeavor mining ESTs and expression data to elucidate known and de-novo GeneCards/spl reg/ genes , 2004, Proceedings. 2004 IEEE Computational Systems Bioinformatics Conference, 2004. CSB 2004..

[27]  Yusuke Nakamura,et al.  Genome-wide profiling of gene expression in 29 normal human tissues with a cDNA microarray. , 2002, DNA research : an international journal for rapid publication of reports on genes and genomes.

[28]  Blatt,et al.  Superparamagnetic clustering of data. , 1998, Physical review letters.

[29]  Guoying Liu,et al.  NetAffx: Affymetrix probesets and annotations , 2003, Nucleic Acids Res..

[30]  D. Slonim.  From patterns to pathways: gene expression data analysis comes of age , 2002, Nature Genetics.

[31]  J. Warrington,et al.  Comparison of human adult and fetal expression and identification of 535 housekeeping/maintenance genes. , 2000, Physiological genomics.

[32]  William McGinnis,et al.  Evolution of transcription factor function. , 2003, Current opinion in genetics & development.

[33]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[34]  Eric P Hoffman,et al.  A web-accessible complete transcriptome of normal human and DMD muscle , 2002, Neuromuscular Disorders.

[35]  Gregory D. Schuler,et al.  Database resources of the National Center for Biotechnology , 2003, Nucleic Acids Res..

[36]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[37]  Peter M. Haverty,et al.  HugeIndex: a database with visualization tools for high-density oligonucleotide array data from normal human tissues , 2002, Nucleic Acids Res..