PAIRADISE

PAIRADISE detects allele-specific alternative splicing (ASAS) from RNA sequencing (RNA-seq) data by aggregating paired-allele signals across individuals to identify differential splicing associated with genetic variation.

Key Features:

• Allele-specific alternative splicing (ASAS) detection: Identifies differential alternative splicing events between alleles using RNA-seq data.
• Paired-allele replicate framework: Treats the two alleles of an individual as paired samples for within-individual comparison.
• Population-scale aggregation: Aggregates ASAS signals across multiple individuals rather than analyzing each sample in isolation.
• Heterozygous SNP-based replication: Considers multiple individuals who share a heterozygous single nucleotide polymorphism (SNP) as replicates.
• Statistical formulation: Frames ASAS detection as a statistical problem using paired replicates to identify differential splicing.
• Compatibility with replicate RNA-seq data: Applicable to replicate RNA-seq data from a single individual or across many individuals.
• Detection of rare variant effects: Capable of detecting the effects of rare genetic variants on alternative splicing.
• Association with GWAS signals: Identifies ASAS events that are associated with genome-wide association study (GWAS) signals for complex traits or diseases.
• Validation by simulation: Demonstrated superior performance compared to alternative statistical models in simulation studies.

Scientific Applications:

• ASAS discovery: Detects allele-specific alternative splicing events in individual-level and population-scale RNA-seq datasets.
• Genetic association interpretation: Links ASAS events to genome-wide association study (GWAS) signals for complex traits and diseases.
• Rare variant impact analysis: Identifies the effects of rare genetic variants on alternative splicing.
• Population transcriptome variation: Facilitates analysis of how genetic variation influences splicing across populations.

Methodology:

Treats two alleles as paired samples, considers multiple individuals sharing a heterozygous SNP as replicates, and formulates ASAS detection as a statistical test aggregating RNA-seq signals across paired replicates.