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

TitleThe effects of death and post-mortem cold ischemia on human tissue transcriptomes.
Publication TypeJournal Article
Year of Publication2018
AuthorsFerreira, PG, Muñoz-Aguirre, M, Reverter, F, Godinho, CPSá, Sousa, A, Amadoz, A, Sodaei, R, Hidalgo, MR, Pervouchine, D, Carbonell-Caballero, J, Nurtdinov, R, Breschi, A, Amador, R, Oliveira, P, Cubuk, C, Curado, J, Aguet, F, Oliveira, C, Dopazo, J, Sammeth, M, Ardlie, KG, Guigó, R
JournalNat Commun
Date Published2018 02 13
KeywordsBlood; Cold Ischemia; Death; Female; gene expression; Humans; Models, Biological; Postmortem Changes; RNA, Messenger; Stochastic Processes; Transcriptome

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.

Alternate JournalNat Commun
PubMed ID29440659
PubMed Central IDPMC5811508
Grant List294653 / / European Research Council / International
U41 HG009494 / HG / NHGRI NIH HHS / United States
R01 MH101814 / MH / NIMH NIH HHS / United States