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Quality control parameters on a large dataset of regionally dissected human control brains for whole genome expression studies
Open accessAbstract
We are building an open-access database of regional human brain expression designed to allow the genome-wide assessment of genetic variability on expression. Array and RNA sequencing technologies make assessment of genome-wide expression possible. Human brain tissue is a challenging source for this work because it can only be obtained several and variable hours post-mortem and after varying agonal states. These variables alter RNA integrity in a complex manner. In this report, we assess the effect of post-mortem delay, agonal state and age on gene expression, and the utility of pH and RNA integrity number as predictors of gene expression as measured on 1266 Affymetrix Exon Arrays. We assessed the accuracy of the array data using QuantiGene, as an independent non-PCR-based method. These quality control parameters will allow database users to assess data accuracy. We report that within the parameters of this study post-mortem delay, agonal state and age have little impact on array quality, array data are robust to variable RNA integrity, and brain pH has only a small effect on array performance. QuantiGene gave very similar expression profiles as array data. This study is the first step in our initiative to make human, regional brain expression freely available.
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“Expression profiling during human brain aging is particularly challenging since it can take hours to days before postmortem tissue is stabilized (Melé et al., 2015; Soreq et al., 2017; Trabzuni et al., 2011).”
From Atlas of the aging mouse brain reveals white matter as vulnerable foci (2023) · cites this paper as Trabzuni et al., 2011
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BackgroundSelf-citation
Research works printed but not linked: 1
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Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409
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MethodInfluentialSelf-citationGene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
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Self-citationGenetic variability in the regulation of gene expression in ten regions of the human brain
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Metadata
- Authors
- Trabzuni, D., Ryten, M., Walker, R., Smith, C., Imran, S., Ramasamy, A., Weale, M. E., & Hardy, J.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- University of Edinburgh (GB)
- Guy's Hospital (GB)
- Corresponding author
- Hardy, John
- ORCID
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2011-09-20
- Volume
- 119
- Issue
- 2
- Pages
- 275-282
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- PMC
- PMC3664422
- OpenAlex
- W2066399252
- Cited by
- 229
- References
- 36
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 10 · 2022: 10 · 2021: 22 · 2020: 13 · 2019: 24 · 2018: 23 · 2017: 25 · 2016: 24 · 2015: 20 · 2014: 16 · 2013: 14 · 2012: 9
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurochemistry (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (089698)
- King Faisal Specialist Hospital and Research Centre
- Medical Research Council (MC_G1000735)
- Army Research Office
- 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 delay, agonal state, brain age, RNA integrity number, brain pH
- MeSH terms
- Adolescent, Adult, Aged, Aging, Brain Chemistry, Cause of Death, Exons, Female, United Kingdom, Humans, Hydrogen-Ion Concentration, Male, Middle Aged, Quality Control, RNA, Sex Characteristics, Tissue Banks, United States, Reproducibility of Results, DNA, Complementary, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Databases, Genetic, Microarray Analysis, Young Adult
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