VDJPuzzle

VDJPuzzle reconstructs productive, full-length B-cell receptor (BCR) sequences from single-cell RNA sequencing (scRNA-seq) data to enable characterization of BCR repertoires and somatic mutations.

Key Features:

• Reconstruction of Full-Length BCR Sequences: Reconstructs productive heavy and light chain BCR sequences from scRNA-seq data.
• Somatic Mutation Identification: Identifies somatic mutations within the VDJ region of BCR sequences.
• Simultaneous Chain and Transcriptomic Capture: Captures both heavy and light chains simultaneously along with their transcriptomic signatures.
• High Success Rate: Demonstrated reconstruction success rates of 100% (n=117) for human B cells and 96.5% (n=200) for murine B cells.
• Validation with Sanger Sequencing: Reconstructed sequences were validated using single-cell Sanger sequencing.

Scientific Applications:

• Immunological Research: Characterizing how B cells adapt via V(D)J recombination and somatic hypermutation.
• Disease Mechanisms: Investigating autoimmune diseases, infections, and cancers where BCR diversity influences pathology.
• Vaccine Development: Analyzing single-cell immune responses to inform vaccine design and efficacy.

Methodology:

Processes scRNA-seq data using bioinformatics algorithms to reconstruct productive full-length BCR heavy and light chains, identify somatic mutations in the VDJ region, and capture associated transcriptomic signatures.