Human Genomics. The Human Transcriptome Across Tissues and Individuals

Overview

Journal Science

Specialty Science

Date 2015 May 9

PMID 25954002

Citations 694

Authors

Marta Mele

Pedro G Ferreira

Ferran Reverter

David S DeLuca

Jean Monlong

Michael Sammeth

Taylor R Young

Jakob M Goldmann

Dmitri D Pervouchine

Timothy J Sullivan

Rory Johnson

Ayellet V Segre

Sarah Djebali

Anastasia Niarchou

Fred A Wright

Tuuli Lappalainen

Miquel Calvo

Gad Getz

Emmanouil T Dermitzakis

Kristin G Ardlie

Roderic Guigo

Affiliations

Soon will be listed here.

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.

Citing Articles

Comparative analysis of genotype imputation strategies for SNPs calling from RNA-seq.

Guo K, Zhong Z, Zeng H, Zhang C, Chitotombe T, Teng J BMC Genomics. 2025; 26(1):245.

PMID: 40082746 PMC: 11907794. DOI: 10.1186/s12864-025-11411-5.

A systematic benchmark of Nanopore long-read RNA sequencing for transcript-level analysis in human cell lines.

Chen Y, Davidson N, Kei Wan Y, Yao F, Su Y, Gamaarachchi H Nat Methods. 2025; .

PMID: 40082608 DOI: 10.1038/s41592-025-02623-4.

An Ocular Gene-Set Expression Library for Heritability Partition and Cell Line Enrichment Analyses.

Hysi P, Hammond C Invest Ophthalmol Vis Sci. 2025; 66(3):11.

PMID: 40042876 PMC: 11892535. DOI: 10.1167/iovs.66.3.11.

Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics.

Velz J, Freudenmann L, Medici G, Dubbelaar M, Mohme M, Ghasemi D Nat Commun. 2025; 16(1):1364.

PMID: 39904979 PMC: 11794601. DOI: 10.1038/s41467-025-56268-0.

Coordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex.

Porter R, An S, Gavilan M, Nagai M, Murata-Nakamura Y, Zhou B Cell Rep. 2025; 44(1):115213.

PMID: 39817906 PMC: 11864812. DOI: 10.1016/j.celrep.2024.115213.

References

Lukk M, Kapushesky M, Nikkila J, Parkinson H, Goncalves A, Huber W . A global map of human gene expression. Nat Biotechnol. 2010; 28(4):322-4. PMC: 2974261. DOI: 10.1038/nbt0410-322. View

. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science. 2015; 348(6235):648-60. PMC: 4547484. DOI: 10.1126/science.1262110. View

Regitz-Zagrosek V, Seeland U . Sex and gender differences in myocardial hypertrophy and heart failure. Wien Med Wochenschr. 2011; 161(5-6):109-16. DOI: 10.1007/s10354-011-0892-8. View

Birdsill A, Walker D, Lue L, Sue L, Beach T . Postmortem interval effect on RNA and gene expression in human brain tissue. Cell Tissue Bank. 2010; 12(4):311-8. PMC: 3343031. DOI: 10.1007/s10561-010-9210-8. View

DeLuca D, Levin J, Sivachenko A, Fennell T, Nazaire M, Williams C . RNA-SeQC: RNA-seq metrics for quality control and process optimization. Bioinformatics. 2012; 28(11):1530-2. PMC: 3356847. DOI: 10.1093/bioinformatics/bts196. View

Ezkurdia I, Del Pozo A, Frankish A, Rodriguez J, Harrow J, Ashman K . Comparative proteomics reveals a significant bias toward alternative protein isoforms with conserved structure and function. Mol Biol Evol. 2012; 29(9):2265-83. PMC: 3424414. DOI: 10.1093/molbev/mss100. View

Harrow J, Frankish A, Gonzalez J, Tapanari E, Diekhans M, Kokocinski F . GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012; 22(9):1760-74. PMC: 3431492. DOI: 10.1101/gr.135350.111. View

. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012; 489(7414):57-74. PMC: 3439153. DOI: 10.1038/nature11247. View

Djebali S, Davis C, Merkel A, Dobin A, Lassmann T, Mortazavi A . Landscape of transcription in human cells. Nature. 2012; 489(7414):101-8. PMC: 3684276. DOI: 10.1038/nature11233. View

10.

Grundberg E, Small K, Hedman A, Nica A, Buil A, Keildson S . Mapping cis- and trans-regulatory effects across multiple tissues in twins. Nat Genet. 2012; 44(10):1084-9. PMC: 3784328. DOI: 10.1038/ng.2394. View

11.

Kelly R, Mahmud A, McKenzie M, Trounce I, St John J . Mitochondrial DNA copy number is regulated in a tissue specific manner by DNA methylation of the nuclear-encoded DNA polymerase gamma A. Nucleic Acids Res. 2012; 40(20):10124-38. PMC: 3488228. DOI: 10.1093/nar/gks770. View

12.

. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013; 45(6):580-5. PMC: 4010069. DOI: 10.1038/ng.2653. View

13.

Lappalainen T, Sammeth M, Friedlander M, t Hoen P, Monlong J, Rivas M . Transcriptome and genome sequencing uncovers functional variation in humans. Nature. 2013; 501(7468):506-11. PMC: 3918453. DOI: 10.1038/nature12531. View

14.

Pickrell J, Pai A, Gilad Y, Pritchard J . Noisy splicing drives mRNA isoform diversity in human cells. PLoS Genet. 2010; 6(12):e1001236. PMC: 3000347. DOI: 10.1371/journal.pgen.1001236. View

15.

Yan M, Wang L, Hymowitz S, Schilbach S, Lee J, Goddard A . Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors. Science. 2000; 290(5491):523-7. DOI: 10.1126/science.290.5491.523. View

16.

Forrest A, Kawaji H, Rehli M, Baillie J, de Hoon M, Haberle V . A promoter-level mammalian expression atlas. Nature. 2014; 507(7493):462-70. PMC: 4529748. DOI: 10.1038/nature13182. View

17.

Carninci P, Shibata Y, Hayatsu N, Sugahara Y, Shibata K, Itoh M . Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes. Genome Res. 2000; 10(10):1617-30. PMC: 310980. DOI: 10.1101/gr.145100. View

18.

Brunet J, Tamayo P, Golub T, Mesirov J . Metagenes and molecular pattern discovery using matrix factorization. Proc Natl Acad Sci U S A. 2004; 101(12):4164-9. PMC: 384712. DOI: 10.1073/pnas.0308531101. View

19.

Yeo G, Holste D, Kreiman G, Burge C . Variation in alternative splicing across human tissues. Genome Biol. 2004; 5(10):R74. PMC: 545594. DOI: 10.1186/gb-2004-5-10-r74. View

20.

Carrel L, Willard H . X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005; 434(7031):400-4. DOI: 10.1038/nature03479. View