Identifying and characterising key alternative splicing events in Drosophila development

Area of Science:

• Genomics
• Molecular Biology
• Bioinformatics

Background:

• Complex Metazoans exhibit extensive alternative splicing, leading to multiple protein isoforms per gene.
• Functional genomics faces challenges in annotating these isoforms, exacerbated by RNASeq data and distinguishing functional variants from noise.
• Existing tools for prioritizing isoforms for functional testing are limited.

Purpose of the Study:

• To develop a computational method for ranking protein isoforms based on their functional significance.
• To investigate the functional roles and characteristics of different isoforms within multi-transcript genes.
• To establish a pipeline for annotating alternatively spliced transcripts.

Main Methods:

• Implementation of a Time-course Switch (TS) score using developmental expression profiles from modENCODE.
• Analysis of sequence features and domain/exon gains in isoforms with high TS scores.
• Development of the Transcript Annotations Pipeline for Alternative Splicing (TAPAS) based on the TS score.

Main Results:

• High TS scores correlate with deterministic splicing, functional changes, and acquisition of new domains/exons.
• Functionally significant isoforms are crucial for essential regulatory processes.
• TAPAS effectively identifies functional neighborhoods of potentially interesting isoforms.

Conclusions:

• A subset of protein isoforms with high functional significance, particularly in regulation, has been identified.
• Novel methods utilizing transcript expression profiles enable better isoform-specific function annotation.
• The developed tools enhance the characterization of alternative splicing's regulatory functions.