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

• DOI: 10.1038/s41467-017-02772-x
• Publication Date: 2018-01-30T10:03:34Z
• Authors: 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-Ca...; Ramil Nurtdinov; Alessandra Breschi; Raziel Amador; Patrícia Oliveira; Cankut Çubuk; João Curado; François Aguet; Carla Oliveira; Joaquin Dopazo; Michael Sammeth; Kristin G. Ardlie; Roderic Guigó
• Keywords: Science; Àcid ribonucleic; Gene Expression; Models, Biological; RNA, Messenger / metabolismo; Article; 03 medical and health sciences; Aprenentatge automàtic; Humans; RNA, Messenger; Stochastic Processes; 0303 health sciences; RNA, Messenger / genetics; Q; Cold Ischemia; Genomics; Expressió gènica; 3. Good health; Death; Genòmica; Blood; Postmortem Changes; RNA; Female; Mineria de dades; Transcriptome

AbstractPost-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.