ASpediaFI: Functional Interaction Analysis of Alternative Splicing Events.

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Alternative splicing (AS) significantly impacts biological processes, phenotypes, and diseases.
• Current differential AS (DAS) gene test methods are limited in delineating the biological relevance of identified events.
• High-throughput datasets require advanced tools for comprehensive AS event analysis.

Purpose of the Study:

• To develop a novel application, Alternative Splicing Encyclopedia: Functional Interaction (ASpediaFI), for systemic identification of DAS events, co-regulated genes, and pathways.
• To establish a heterogeneous interaction network integrating genes, AS events, and pathways.
• To evaluate ASpediaFI's performance against existing methods using simulated and public datasets.

Main Methods:

• ASpediaFI constructs a heterogeneous interaction network connecting genes, AS events, and pathways via co-expression and pathway knowledge.
• The random walk with restart algorithm is employed to explore the network and identify significant AS events, genes, and pathways based on query gene sets.
• Performance evaluation involved simulated RNA sequencing (RNA-seq) datasets and analysis of three public cancer datasets.

Main Results:

• ASpediaFI demonstrated strong performance in both simulated and real-world cancer datasets.
• The integrative approach revealed that DAS events, when considered within a global co-expression network and relevant pathways, are crucial for determining the functional importance of spliced genes.
• ASpediaFI successfully identified biologically relevant candidates in public cancer datasets.

Conclusions:

• ASpediaFI provides a powerful, integrative approach for identifying functionally relevant AS events and co-regulated genes.
• The tool enhances the understanding of how differential splicing contributes to biological processes and diseases.
• ASpediaFI is publicly available, facilitating broader research in splicing and gene regulation.