Reconstructing and mining the B cell repertoire with ImmunediveRsity.

Area of Science:

• Immunology
• Bioinformatics
• Computational Biology

Background:

• The B cell antigen receptor repertoire is diverse and shaped by clonal selection.
• High-throughput DNA sequencing (HTS) of lymphocyte repertoires (Rep-Seq) aids in exploring this diversity.
• Tools for reconstructing and analyzing antibody sequences are crucial for understanding immune responses.

Purpose of the Study:

• To develop an integrated pipeline for comprehensive analysis of B cell repertoire data from HTS.
• To enable repertoire reconstruction, quality filtering, and noise correction.
• To facilitate sample comparison and mining for antigen-specific antibodies.

Main Methods:

• Developed ImmunediveRity, a stand-alone pipeline using R programming, GNU software, and custom scripts.
• Implemented V(D)J segment assignment, clonal origin determination, and unique heavy chain identification.
• Utilized HTS data from human and mouse samples, including immunized mice, for validation.

Main Results:

• ImmuliveRity successfully reconstructs B cell repertoires and identifies clonal structures.
• The pipeline provides repertoire metrics and graphical outputs for comparative analysis.
• Analysis of immunized mice revealed distinct clonal diversity patterns in IgM and IgG compartments, identifying known antigen-specific antibodies.

Conclusions:

• ImmuliveRity offers significant advantages for B cell repertoire analysis and mining compared to existing tools.
• The pipeline is open-source, free for academic use, and compatible with GNU/Linux and MacOS.
• ImmuliveRity facilitates the identification of antigen-specific antibodies and exploration of immune repertoire dynamics.