Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequently employed to pool local results. However, the accuracy might drop if class labels are inhomogeneously distributed among cohorts. Flimma ( https://exbio.wzw.tum.de/flimma/ ) addresses this issue by implementing the state-of-the-art workflow limma voom in a federated manner, i.e., patient data never leaves its source site. Flimma results are identical to those generated by limma voom on aggregated datasets even in imbalanced scenarios where meta-analysis approaches fail.
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http://dx.doi.org/10.1186/s13059-021-02553-2 | DOI Listing |
Genome Biol
October 2024
Department of Statistics and Data Science, University of California, Los Angeles, CA, 90095, USA.
Two correspondences raised concerns or comments about our analyses regarding exaggerated false positives found by differential expression (DE) methods. Here, we discuss the points they raise and explain why we agree or disagree with these points. We add new analysis to confirm that the Wilcoxon rank-sum test remains the most robust method compared to the other five DE methods (DESeq2, edgeR, limma-voom, dearseq, and NOISeq) in two-condition DE analyses after considering normalization and winsorization, the data preprocessing steps discussed in the two correspondences.
View Article and Find Full Text PDFGenome Biol
September 2024
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
Missing covariate data is a common problem that has not been addressed in observational studies of gene expression. Here, we present a multiple imputation method that accommodates high dimensional gene expression data by incorporating principal component analysis of the transcriptome into the multiple imputation prediction models to avoid bias. Simulation studies using three datasets show that this method outperforms complete case and single imputation analyses at uncovering true positive differentially expressed genes, limiting false discovery rates, and minimizing bias.
View Article and Find Full Text PDFGenomics
September 2024
Department of Psychiatry, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA; Section of Biomedical Genetics, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. Electronic address:
Prolonged alcohol consumption can disturb the expression of both coding and noncoding genes in the brain. These dysregulated genes may co-express in modules and interact within networks, consequently influencing the susceptibility to developing alcohol use disorder (AUD). In the present study, we performed an RNA-seq analysis of the expression of both long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in 192 postmortem tissue samples collected from eight brain regions (amygdala, caudate nucleus, cerebellum, hippocampus, nucleus accumbens, prefrontal cortex, putamen, and ventral tegmental area) of 12 AUD and 12 control subjects of European ancestry.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
February 2024
Department of Population Medicine, Harvard Medical School, Harvard Pilgrim Health Care Institute, Boston, MA 02215, USA.
Context: Elevated body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. The placental transcriptome may elucidate molecular mechanisms underlying these associations.
Objective: We examined the association of first-trimester maternal BMI with the placental transcriptome in the Gen3G prospective cohort.
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