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Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain
Open accessAbstract
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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“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]
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Self-citation
Metadata
- 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
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 55
- Issue
- 4
- Pages
- 346-352
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3098566
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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