Systematic Analysis of Gene Expression Patterns Associated with Postmortem Interval in Human Tissues

Overview

Journal Sci Rep

Specialty Science

Date 2017 Jul 16

PMID 28710439

Citations 56

Authors

Yizhang Zhu

Likun Wang

Yuxin Yin

Ence Yang

Affiliations

Soon will be listed here.

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.

Citing Articles

Spatial Gene Expression of Human Coronary Arteries Revealed the Molecular Features of Diffuse Intimal Thickening in Explanted Hearts.

Li B, Leung S, Elishaev M, Cheng W, Mocci G, Bjorkegren J Int J Mol Sci. 2025; 26(5).

PMID: 40076574 PMC: 11900230. DOI: 10.3390/ijms26051949.

Identification of Hub Genes Involved in Early-onset Schizophrenia: From Genetic Susceptibility to Predicted Regulated Gene Expression.

Jen Y, Yu S, Hsiao P, Kuo P, Liu C, Liu C Res Sq. 2025; .

PMID: 39975901 PMC: 11838744. DOI: 10.21203/rs.3.rs-5833160/v1.

The Human Microglia Atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions.

Martins-Ferreira R, Calafell-Segura J, Leal B, Rodriguez-Ubreva J, Martinez-Saez E, Mereu E Nat Commun. 2025; 16(1):739.

PMID: 39820004 PMC: 11739505. DOI: 10.1038/s41467-025-56124-1.

Considerations for building and using integrated single-cell atlases.

Hrovatin K, Sikkema L, Shitov V, Heimberg G, Shulman M, Oliver A Nat Methods. 2024; 22(1):41-57.

PMID: 39672979 DOI: 10.1038/s41592-024-02532-y.

Time-dependent changes in genome-wide gene expression and post-transcriptional regulation across the post-death process in silkworm.

Yang L, Tang D, Luo S, Li W, Jiang Y, Lin L DNA Res. 2024; 31(6).

PMID: 39546332 PMC: 11605879. DOI: 10.1093/dnares/dsae031.

References

Gopee N, Howard P . A time course study demonstrating RNA stability in postmortem skin. Exp Mol Pathol. 2006; 83(1):4-10. DOI: 10.1016/j.yexmp.2006.11.001. View

Pittner S, Ehrenfellner B, Zissler A, Racher V, Trutschnig W, Bathke A . First application of a protein-based approach for time since death estimation. Int J Legal Med. 2016; 131(2):479-483. PMC: 5591615. DOI: 10.1007/s00414-016-1459-4. View

Sato K, Kawashima S . Calpain function in the modulation of signal transduction molecules. Biol Chem. 2001; 382(5):743-51. DOI: 10.1515/BC.2001.090. View

Gallego Romero I, Pai A, Tung J, Gilad Y . RNA-seq: impact of RNA degradation on transcript quantification. BMC Biol. 2014; 12:42. PMC: 4071332. DOI: 10.1186/1741-7007-12-42. View

Mele M, Ferreira P, Reverter F, DeLuca D, Monlong J, Sammeth M . Human genomics. The human transcriptome across tissues and individuals. Science. 2015; 348(6235):660-5. PMC: 4547472. DOI: 10.1126/science.aaa0355. View

Yang J, Huang T, Petralia F, Long Q, Zhang B, Argmann C . Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases. Sci Rep. 2015; 5:15145. PMC: 4609956. DOI: 10.1038/srep15145. View

Mackenzie I, Neumann M . Molecular neuropathology of frontotemporal dementia: insights into disease mechanisms from postmortem studies. J Neurochem. 2016; 138 Suppl 1:54-70. DOI: 10.1111/jnc.13588. View

Ervin J, Heinzen E, Cronin K, Goldstein D, Szymanski M, Burke J . Postmortem delay has minimal effect on brain RNA integrity. J Neuropathol Exp Neurol. 2007; 66(12):1093-9. DOI: 10.1097/nen.0b013e31815c196a. View

Gupta S, Halushka M, Hilton G, Arking D . Postmortem cardiac tissue maintains gene expression profile even after late harvesting. BMC Genomics. 2012; 13:26. PMC: 3342086. DOI: 10.1186/1471-2164-13-26. View

10.

Brinkmeyer-Langford C, Guan J, Ji G, Cai J . Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains. Front Aging Neurosci. 2016; 8:183. PMC: 4971101. DOI: 10.3389/fnagi.2016.00183. View

11.

Sobue S, Sakata K, Sekijima Y, Qiao S, Murate T, Ichihara M . Characterization of gene expression profiling of mouse tissues obtained during the postmortem interval. Exp Mol Pathol. 2016; 100(3):482-92. DOI: 10.1016/j.yexmp.2016.05.007. View

12.

Samarasekera N, Salman R, Huitinga I, Klioueva N, McLean C, Kretzschmar H . Brain banking for neurological disorders. Lancet Neurol. 2013; 12(11):1096-105. DOI: 10.1016/S1474-4422(13)70202-3. View

13.

Gonzalez-Herrera L, Valenzuela A, Marchal J, Lorente J, Villanueva E . Studies on RNA integrity and gene expression in human myocardial tissue, pericardial fluid and blood, and its postmortem stability. Forensic Sci Int. 2013; 232(1-3):218-28. DOI: 10.1016/j.forsciint.2013.08.001. View

14.

Houseley J, Tollervey D . The many pathways of RNA degradation. Cell. 2009; 136(4):763-76. DOI: 10.1016/j.cell.2009.01.019. View

15.

Ferreira M, Cunha E . Can we infer post mortem interval on the basis of decomposition rate? A case from a Portuguese cemetery. Forensic Sci Int. 2013; 226(1-3):298.e1-6. DOI: 10.1016/j.forsciint.2013.01.006. View

16.

Tourriere H, Chebli K, Tazi J . mRNA degradation machines in eukaryotic cells. Biochimie. 2002; 84(8):821-37. DOI: 10.1016/s0300-9084(02)01445-1. View

17.

Schroeder A, Mueller O, Stocker S, Salowsky R, Leiber M, Gassmann M . The RIN: an RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006; 7:3. PMC: 1413964. DOI: 10.1186/1471-2199-7-3. View

18.

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

19.

. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013; 45(6):580-5. PMC: 4010069. DOI: 10.1038/ng.2653. View

20.

Partemi S, Berne P, Batlle M, Berruezo A, Mont L, Riuro H . Analysis of mRNA from human heart tissue and putative applications in forensic molecular pathology. Forensic Sci Int. 2010; 203(1-3):99-105. DOI: 10.1016/j.forsciint.2010.07.005. View