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Published on: January 17, 2019
Systematic analysis of gene expression patterns associated with postmortem interval in human tissues
Yizhang Zhu1,2, Likun Wang1, Yuxin Yin3,4
1Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Abstract:
Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues. A key factor in this process is the postmortem interval (PMI), which is defined as the interval between death and sample collection. However, global patterns of postmortem mRNA degradation at individual gene levels across diverse human tissues remain largely unknown. In this study, we performed a systematic analysis of alteration of gene expression associated with PMI in human tissues. From the Genotype-Tissue Expression (GTEx) database, we evaluated gene expression levels of 2,016 high-quality postmortem samples from 316 donors of European descent, with PMI ranging from 1 to 27 hours. We found that PMI-related mRNA degradation is tissue-specific, gene-specific, and even genotype-dependent, thus drawing a more comprehensive picture of PMI-associated gene expression across diverse human tissues. Additionally, we also identified 266 differentially variable (DV) genes, such as DEFB4B and IFNG, whose expression is significantly dispersed between short PMI (S-PMI) and long PMI (L-PMI) groups. In summary, our analyses provide a comprehensive profile of PMI-associated gene expression, which will help interpret gene expression patterns in the evaluation of postmortem tissues.
Insights
Postmortem mRNA degradation varies by tissue, gene, and genotype. Understanding the postmortem interval (PMI) is crucial for accurate gene expression research in human tissues.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Postmortem mRNA degradation poses challenges for gene expression research using human tissues.
- The postmortem interval (PMI) is a critical factor influencing mRNA stability.
- Comprehensive understanding of global gene expression changes related to PMI across human tissues is limited.
Purpose of the Study:
- To systematically analyze gene expression alterations associated with PMI in diverse human tissues.
- To characterize the tissue-specific, gene-specific, and genotype-dependent patterns of postmortem mRNA degradation.
- To identify genes with significant expression variability between short and long PMI groups.
Main Methods:
- Utilized the Genotype-Tissue Expression (GTEx) database.
- Analyzed gene expression levels from 2,016 high-quality postmortem samples across 316 donors.
- Examined samples with postmortem intervals ranging from 1 to 27 hours.
Main Results:
- Postmortem mRNA degradation exhibits significant tissue-specific, gene-specific, and genotype-dependent patterns.
- Identified 266 differentially variable (DV) genes, including DEFB4B and IFNG, showing distinct expression between short and long PMI groups.
- Provided a detailed profile of PMI-associated gene expression across various human tissues.
Conclusions:
- The study offers a comprehensive overview of how PMI affects gene expression in human postmortem tissues.
- Findings aid in the interpretation of gene expression data from postmortem samples.
- Highlights the importance of considering PMI and its interacting factors in gene expression studies.
