qSVA framework for RNA quality correction in differential expression analysis
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Abstract
Significance: Many studies use measurements of gene expression in human postmortem and ex vivo tissues like brain and blood to characterize genomic correlates of illness. However, molecular analyses of these tissues can be susceptible to a wide range of confounders that may be difficult to measure and remove. In this article, we describe an analysis framework for identifying and removing previously uncharacterized quality biases in measurements of RNA. Our paper critically highlights the shortcomings of standard RNA quality correction approaches, such as statistically adjusting for RNA integrity numbers. We show that the our framework removes residual confounding by RNA quality and greatly improves replication of significant differentially expressed genes across independent datasets by more than threefold compared with previous approaches.
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Differential expression results did not overlap with RNA degradation metrics, indicating they were not driven by RNA-quality confounds.
“Differential expression did not overlap with experimentally defined RNA degradation metrics in brain, indicating that results were not driven by RNA-quality confounds (Fig S4) (22).”
From Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder (2018) · cites this paper as [22]
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- Authors
- Jaffe, A. E., Tao, R., Norris, A. L., Kealhofer, M., Nellore, A., Shin, J. H., Kim, D., Jia, Y., Hyde, T. M., Kleinman, J. E., Straub, R. E., Leek, J. T., & Weinberger, D. R.
- Affiliations
- Johns Hopkins University (US)
- Kennedy Krieger Institute (US)
- Corresponding author
- Jaffe, Andrew E.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-06-20
- Volume
- 114
- Issue
- 27
- Pages
- 7130-7135
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5502589
- OpenAlex
- W2681631427
- Cited by
- 114
- References
- 35
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 8 · 2023: 13 · 2022: 19 · 2021: 11 · 2020: 12 · 2019: 15 · 2018: 16 · 2017: 4
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (R21MH109956)
- HHS | NIH | National Institute of General Medical Sciences (R01GM105705)
- Lieber Institute for Brain Development (Internal Funds)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- RNA quality, RNA degradation, confounding adjustment, differential expression analysis, postmortem brain, schizophrenia, replication rate, transcriptomics
- MeSH terms
- Algorithms, Animals, DNA Replication, Gene Expression Regulation, Genotype, Humans, RNA, Schizophrenia, Sequence Analysis, RNA, Computational Biology, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Transcriptome, Gray Matter
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