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

Pedro G. Ferreira (), Manuel Muñoz-Aguirre, Ferran Reverter, Caio P. Sá Godinho, Abel Sousa, Alicia Amadoz, Reza Sodaei, Marta R. Hidalgo, Dmitri Pervouchine, Jose Carbonell-Caballero, Ramil Nurtdinov, Alessandra Breschi, Raziel Amador, Patrícia Oliveira, Cankut Çubuk, João Curado, François Aguet, Carla Oliveira, Joaquin Dopazo, Michael Sammeth, Kristin G. Ardlie and Roderic Guigó ()
Additional contact information
Pedro G. Ferreira: Universidade do Porto
Manuel Muñoz-Aguirre: The Barcelona Institute for Science and Technology
Ferran Reverter: The Barcelona Institute for Science and Technology
Caio P. Sá Godinho: Federal University of Rio de Janeiro (UFRJ)
Abel Sousa: Universidade do Porto
Alicia Amadoz: Igenomix S.A
Reza Sodaei: The Barcelona Institute for Science and Technology
Marta R. Hidalgo: Hospital Virgen del Rocio
Dmitri Pervouchine: The Barcelona Institute for Science and Technology
Jose Carbonell-Caballero: The Barcelona Institute of Science and Technology, PRBB
Ramil Nurtdinov: The Barcelona Institute for Science and Technology
Alessandra Breschi: The Barcelona Institute for Science and Technology
Raziel Amador: The Barcelona Institute for Science and Technology
Patrícia Oliveira: Universidade do Porto
Cankut Çubuk: Hospital Virgen del Rocio
João Curado: The Barcelona Institute for Science and Technology
François Aguet: The Broad Institute of MIT and Harvard
Carla Oliveira: Universidade do Porto
Joaquin Dopazo: Igenomix S.A
Michael Sammeth: Federal University of Rio de Janeiro (UFRJ)
Kristin G. Ardlie: The Broad Institute of MIT and Harvard
Roderic Guigó: The Barcelona Institute for Science and Technology

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02772-x

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