Slinker

Slinker visualizes sample-specific superTranscripts and RNA-Seq alignments to reveal novel splicing events and transcriptome variations relevant to disease.

Key Features:

• Implementation: Implemented in Python and Bpipe for pipeline orchestration.
• Sample-specific superTranscript assembly: Uses a data-driven approach to assemble sample-specific superTranscripts from RNA-Seq data.
• Transcript assembly engine: Utilizes Stringtie2 for transcript assembly, enabling capture of sequences across any gene including those not annotated in reference genomes.
• Merging and conversion: Merges assembled transcripts with reference transcripts and converts the result into superTranscripts.
• Visualization: Generates interactive visualizations using Plotly that incorporate annotation and coverage information.
• Sparsity-aware analysis: Addresses sparsity of RNA-Seq mapping to exons and enables visualization and analysis across introns and other sparse regions.

Scientific Applications:

• Novel splicing discovery: Identification of novel splicing events that may be implicated in pathogenic phenotypes.
• Rare disease validation: Applied to and validated on five novel splicing events in rare disease samples from a cohort with primary muscular disorders.
• Tumor transcriptome analysis: Visualization of deletion events in tumor transcriptomes, specifically exemplified for the leukemia gene IKZF1.
• Splicing variation analysis: Facilitates analysis of splicing variations across sparse genomic regions such as introns.

Methodology:

Implemented in Python and Bpipe; uses Stringtie2 for transcript assembly, merges assembled transcripts with reference transcripts, converts merged transcripts into superTranscripts, and generates Plotly visualizations including annotation and coverage information.