pairedGSEA

pairedGSEA runs paired Differential Gene Expression (DGE) and Differential Gene Splicing (DGS) analysis to profile transcriptional changes in RNA-seq datasets and identify both shared and distinct biological signals from expression and splicing.

Key Features:

• Paired DGE and DGS Analysis: The package runs paired Differential Gene Expression (DGE) and Differential Gene Splicing (DGS) analysis.
• Intermediate Results Storage: The package allows users to store intermediate results for further investigation.
• Over-Representation Analysis (ORA): The package includes a wrapper function for running an Over-Representation Analysis (ORA).
• Plotting Functionalities: The package includes functionalities for plotting the results.

Scientific Applications:

• RNA-seq Transcriptional Profiling: pairedGSEA profiles transcriptional changes in RNA-seq datasets to quantify the relative contributions of expression and splicing changes to biological signals.
• Gene-Set Enrichment Analysis: Gene-set enrichment analysis indicates that expression and splicing both convey shared and distinct biological signals.
• Alternative Splicing Biology: The tool establishes alternative splicing as a major regulator of the human condition and supports the transition from a gene-centric to an isoform-centric research paradigm.

Methodology:

pairedGSEA was developed and used to profile transcriptional changes in 100 representative RNA-seq datasets. Systematic analysis demonstrated that changes in splicing, on average, contribute to 48.1% of the biological signal in expression analyses.