CorrAdjust unveils biologically relevant transcriptomic correlations by efficiently eliminating hidden confounders.
Publication/Presentation Date
5-22-2025
Abstract
Correcting for confounding variables is often overlooked when computing RNA-RNA correlations, even though it can profoundly affect results. We introduce CorrAdjust, a method for identifying and correcting such hidden confounders. CorrAdjust selects a subset of principal components to residualize from expression data by maximizing the enrichment of "reference pairs" among highly correlated RNA-RNA pairs. Unlike traditional machine learning metrics, this novel enrichment-based metric is specifically designed to evaluate correlation data and provides valuable RNA-level interpretability. CorrAdjust outperforms current state-of-the-art methods when evaluated on 25 063 human RNA-seq datasets from The Cancer Genome Atlas, the Genotype-Tissue Expression project, and the Geuvadis collection. In particular, CorrAdjust excels at integrating small RNA and mRNA sequencing data, significantly enhancing the enrichment of experimentally validated miRNA targets among negatively correlated miRNA-mRNA pairs. CorrAdjust, with accompanying documentation and tutorials, is available at https://tju-cmc-org.github.io/CorrAdjust.
Volume
53
Issue
10
ISSN
1362-4962
Published In/Presented At
Nersisyan, S., Loher, P., & Rigoutsos, I. (2025). CorrAdjust unveils biologically relevant transcriptomic correlations by efficiently eliminating hidden confounders. Nucleic acids research, 53(10), gkaf444. https://doi.org/10.1093/nar/gkaf444
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
40448503
Department(s)
Administration and Leadership
Document Type
Article