title: Human genomics. The human transcriptome across tissues and individuals.
abstract: Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes—which is most clearly seen in blood—though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Harvard Department of stem cell and regenerative biology, Harvard University, Cambridge, MA, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Melé
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Ferreira
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Reverter
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: DeLuca
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. McGill University, Montreal, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Monlong
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. National Institute for Scientific Computing (LNCC), Petropolis, Rio de Janeiro, Brazil.
authors.forename: Michael
authors.initials: M
authors.lastname: Sammeth
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Taylor R
authors.initials: TR
authors.lastname: Young
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Radboud University, Nijmegen, Netherlands.
authors.forename: Jakob M
authors.initials: JM
authors.lastname: Goldmann
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskie Gory 1-73, 119992 Moscow, Russia.
authors.forename: Dmitri D
authors.initials: DD
authors.lastname: Pervouchine
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sullivan
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Rory
authors.initials: R
authors.lastname: Johnson
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: Ayellet V
authors.initials: AV
authors.lastname: Segrè
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain.
authors.forename: Sarah
authors.initials: S
authors.lastname: Djebali
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Niarchou
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Harvard Department of stem cell and regenerative biology, Harvard University, Cambridge, MA, USA. Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland. Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Broad Institute of MIT and Harvard, Cambridge, MA, USA. McGill University, Montreal, Canada. National Institute for Scientific Computing (LNCC), Petropolis, Rio de Janeiro, Brazil. Radboud University, Nijmegen, Netherlands. Faculty of Bioengineering and Bioinformatics, Moscow State University, Leninskie Gory 1-73, 119992 Moscow, Russia. North Carolina State University, Raleigh, NC, USA. New York Genome Center, New York, NY, USA. Department of Systems Biology, Columbia University, New York, NY, USA. Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA. Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Catalonia, Spain. Joint CRG-Barcelona Super Computing Center (BSC)-Institut de Recerca Biomedica (IRB) Program in Computational Biology, Barcelona, Catalonia, Spain.
authors.affiliation: North Carolina State University, Raleigh, NC, USA.
authors.forename: Fred A
authors.initials: FA
authors.lastname: Wright
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland. New York Genome Center, New York, NY, USA. Department of Systems Biology, Columbia University, New York, NY, USA.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Lappalainen
authors.affiliation: Facultat de Biologia, Universitat de Barcelona (UB), Barcelona, Catalonia, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Calvo
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA. Cancer Center and Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Gad
authors.initials: G
authors.lastname: Getz
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland. Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland. Swiss Institute of Bioinformatics, Geneva, Switzerland.
authors.forename: Emmanouil T
authors.initials: ET
authors.lastname: Dermitzakis
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA. kardlie@broadinstitute.org roderic.guigo@crg.cat.
authors.forename: Kristin G
authors.initials: KG
authors.lastname: Ardlie
authors.affiliation: Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain. Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Catalonia, Spain. Joint CRG-Barcelona Super Computing Center (BSC)-Institut de Recerca Biomedica (IRB) Program in Computational Biology, Barcelona, Catalonia, Spain. kardlie@broadinstitute.org roderic.guigo@crg.cat.
authors.forename: Roderic
authors.initials: R
authors.lastname: Guigó
mesh_terms: D017398:Alternative Splicing; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017423:Sequence Analysis, RNA; D012737:Sex Factors; D059467:Transcriptome