Format

Send to

Choose Destination
Nat Commun. 2018 Feb 13;9(1):490. doi: 10.1038/s41467-017-02772-x.

The effects of death and post-mortem cold ischemia on human tissue transcriptomes.

Author information

1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal. pferreira@ipatimup.pt.
2
Institute of Molecular Pathology and Immunology, University of Porto, Rua Dr. Roberto Frias s/n, Porto, 4200-625, Portugal. pferreira@ipatimup.pt.
3
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, Barcelona, E-08003, Catalonia, Spain.
4
Universitat Pompeu Fabra (UPF), Barcelona, E-08003, Catalonia, Spain.
5
Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, E-08003, Catalonia, Spain.
6
Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Barcelona, E-08034, Catalonia, Spain.
7
Universitat de Barcelona, Barcelona, E-08028, Catalonia, Spain.
8
Institute of Biophysics Carlos Chagas Filho (IBCCF), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, 21941-902, Brazil.
9
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.
10
Institute of Molecular Pathology and Immunology, University of Porto, Rua Dr. Roberto Frias s/n, Porto, 4200-625, Portugal.
11
European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Cambridge, CB10 1 SD, UK.
12
Department of Bioinformatics, Igenomix S.A, Valencia, 46980, Spain.
13
Clinical Bioinformatics Area, Fundación Progreso y Salud (FPS), Hospital Virgen del Rocio, Sevilla, 41013, Spain.
14
Skolkovo Institute of Science and Technology, 100 Novaya Street, Skolkovo, Moscow Region, 143025, Russia.
15
Chromatin and Gene expression Lab, Gene Regulation, Stem Cells and Cancer Program, Centre de Regulació Genòmica (CRG), The Barcelona Institute of Science and Technology, PRBB, Barcelona, 08003, Spain.
16
The Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
17
Functional Genomics Node (INB), FPS, Hospital Virgen del Rocio, Sevilla, 41013, Spain.
18
Bioinformatics in Rare Diseases (BiER), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), FPS, Hospital Virgen del Rocio, Sevilla, 41013, Spain.
19
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology, Dr. Aiguader 88, Barcelona, E-08003, Catalonia, Spain. roderic.guigo@crg.cat.
20
Universitat Pompeu Fabra (UPF), Barcelona, E-08003, Catalonia, Spain. roderic.guigo@crg.cat.
21
Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, E-08003, Catalonia, Spain. roderic.guigo@crg.cat.

Abstract

Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.

PMID:
29440659
PMCID:
PMC5811508
DOI:
10.1038/s41467-017-02772-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center