Bisbee

Bisbee performs differential splicing analysis, splicing outlier detection, and splice isoform protein sequence prediction from RNA sequencing (RNAseq) data to identify disease-associated splice events and predict their protein-level effects.

Key Features:

• Differential Splicing Analysis: Evaluates differences in the percentages of sequence reads representing local splice events to quantify splicing variation between conditions or groups.
• Splicing Outlier Detection: Employs a novel statistical approach to identify outliers in splicing patterns that may indicate disease-associated alterations.
• Protein-Level Effect Prediction: Predicts splice isoform protein sequences and the protein-level consequences of splice alterations.
• Read-Percentage Testing: Tests for differences in sequence read percentages that represent local splice events as the basis for detecting differential splicing.
• Result Processing Scripts: Includes utility scripts for data extraction, annotation, filtering, and summarization of results.
• Improved Sensitivity and Specificity: Demonstrates enhanced sensitivity and specificity compared to existing methods for detecting splice events.

Scientific Applications:

• Tissue-specific splice variant identification: Validated using matched RNAseq and mass spectrometry data from normal tissues to identify tissue-specific splice variants.
• Mass spectrometry confirmation: Enables predictions that can be confirmed by mass spectrometry.
• Rare disease splicing analysis: Rediscovered previously validated pathogenic splicing variants linked to rare diseases.
• Tumor-specific isoform discovery: Identified tumor-specific splice isoforms associated with oncogenic mutations.
• Melanoma-associated splicing: Detected common tumor-associated splice isoforms replicated across independent melanoma datasets.

Methodology:

Tests for differences in sequence read percentages representing local splice events; employs a novel statistical method for splicing outlier detection; predicts splice isoform protein sequences; and provides utility scripts for data extraction, annotation, filtering, and summarization.