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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8670124PMC
http://dx.doi.org/10.1186/s13059-021-02553-2DOI Listing

Publication Analysis

Top Keywords

limma voom
8
flimma federated
4
federated privacy-aware
4
privacy-aware tool
4
tool differential
4
differential gene
4
gene expression
4
expression analysis
4
analysis aggregating
4
aggregating transcriptomics
4

Similar Publications

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 PDF
Article Synopsis
  • The study investigates the link between metabolic dysfunction-associated steatotic liver disease (MASLD) and immune-mediated inflammatory diseases (IMIDs), finding a higher prevalence of advanced liver disease in IMID patients compared to a matched control group.
  • Utilizing a case-control design, the research analyzed liver biopsy data and RNA sequencing from patients to identify significant differences in gene expression related to liver disease between IMID and control groups.
  • Results indicate that IMIDs not only increase the risk of advanced steatotic liver disease but also suggest a unique pathway for MASLD development in these patients, separate from traditional metabolic factors.
View Article and Find Full Text PDF

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 PDF

Brain lncRNA-mRNA co-expression regulatory networks and alcohol use disorder.

Genomics

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 PDF

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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!