AUTHOR=Dai Jiacheng , Chen Yu , Dai Rujia , Jiang Yi , Tian Jianghua , Liu Sihan , Xu Meng , Li Miao , Zhou Jiaqi , Liu Chunyu , Chen Chao TITLE=Agonal Factors Distort Gene-Expression Patterns in Human Postmortem Brains JOURNAL=Frontiers in Neuroscience VOLUME=15 YEAR=2021 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.614142 DOI=10.3389/fnins.2021.614142 ISSN=1662-453X ABSTRACT=

Agonal factors, the conditions that occur just prior to death, can impact the molecular quality of postmortem brains, influencing gene expression results. Our study used gene expression data of 262 samples from ROSMAP with the detailed terminal state recorded for each donor, such as fever, infection, and unconsciousness. Fever and infection were the primary contributors to brain gene expression changes, brain cell-type-specific gene expression, and cell proportion changes. Furthermore, we also found that previous studies of gene expression in postmortem brains were confounded by agonal factors. Therefore, correction for agonal factors is important in the step of data preprocessing. Our analyses revealed fever and infection contributing to gene expression changes in postmortem brains and emphasized the necessity of study designs that document and account for agonal factors.