Cited by 331Molecular Biology Techniques and ApplicationsGene expression and cancer classificationSingle-cell and spatial transcriptomics

Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain

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Tomita, Hiroaki, Vawter, Marquis P, Walsh, David M, Evans, Simon J, Choudary, Prabhakara V, Li, Jun, Overman, Kevin M, Atz, Mary E +5 more·2004·Biological Psychiatry

Abstract

There are major concerns that specific agonal conditions, including coma and hypoxia, might affect ribonucleic acid (RNA) integrity in postmortem brain studies. We report that agonal factors significantly affect RNA integrity and have a major impact on gene expression profiles in microarrays. In contrast to agonal factors, gender, age, and postmortem factors have less effect on gene expression profiles. The Average Correlation Index is proposed as a method for evaluating RNA integrity on the basis of similarity of microarray profiles. Reducing the variance due to agonal factors is critical in investigating small but validated gene expression differences in messenger RNA levels between psychiatric patients and control subjects.

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Crossref · 10.1016/j.biopsych.2003.10.013

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  • Very few transcriptomic studies provide information on acute premortem variables or cause of death, which may potentially have a much larger effect on RNA quality and gene expression.

    “Additionally, very few transcriptomic studies provide information on acute premortem variables or cause of death, which are particularly important as they may potentially have a much larger effect on RNA quality and gene expression71–76,78–80.”

    From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [74]

    The Abstract and Conclusion report that agonal conditions around death substantially affect RNA integrity and gene-expression profiles, more than postmortem factors do. The paper does not establish that very few transcriptomic studies provide information on acute premortem variables or cause of death; searches for reporting practices found no such assessment. The indexed copy provides no page numbers for these passages. (LLM, conf=0.85)

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  1. Netsky M. Degradation of the Cerebellum and Its Pathways. New York: McGraw Hill; 1968. [Google Scholar]

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Authors
Tomita, H., Vawter, M. P., Walsh, D. M., Evans, S. J., Choudary, P. V., Li, J., Overman, K. M., Atz, M. E., Myers, R. M., Jones, E. G., Watson, S. J., Akil, H., & Bunney, W. E.
Affiliations
  • University of California, Irvine (US)
  • University of Michigan (US)
  • University of California, Davis (US)
  • Stanford University (US)
Corresponding author
Bunney, William E
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2004-02
Volume
55
Issue
4
Pages
346-352
ISSN
0006-3223 (ISSN-L)
OpenAlex
W2134441514
Cited by
331
References
38
Citations by year
2026: 8 · 2025: 10 · 2024: 10 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 10 · 2019: 6 · 2018: 19 · 2017: 11 · 2016: 13 · 2015: 12 · 2014: 11 · 2013: 17 · 2012: 16
FWCI
9.24
Type
journal article
Language
en
Open access
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (P50MH60398, R01MH054844, MH54844, MH 42251, P50MH060398, P01MH042251)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
postmortem brain, gene expression profiles, RNA integrity, microarray quality control, hypoxia, coma, postmortem interval, psychiatric patients
MeSH terms
Adult, Aged, Autopsy, Brain Chemistry, Major Depressive Disorder, Humans, Male, Middle Aged, Postmortem Changes, Quality Control, RNA, Statistics as Topic, Time Factors, Reproducibility of Results, Gene Expression, Case-Control Studies, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling

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