CLIP

CLIP quantifies selection in immunoglobulin sequences from high-throughput sequencing data to analyze somatic hypermutation and antigen-driven selection during B-cell affinity maturation.

Key Features:

• V(D)J Germline Segment Identification: Uses IMGT alignment to identify V(D)J germline segments in immunoglobulin sequences.
• Batch Processing: Supports submission and analysis of multiple sequences simultaneously for large-scale datasets.
• Integration of Test Statistics: Incorporates a Focused binomial test and a Z-score-based statistic to detect selection pressures.
• Comparative Analysis: Enables comparison of selection signals between groups of sequences derived from different germline V(D)J segments.
• Quantitative Framework: Applies Bayesian estimation methods (BASELINe) to quantify antigen-driven selection from somatic mutation patterns.

Scientific Applications:

• Immune response analysis: Detects and quantifies selection in immunoglobulin sequences to study responses to pathogens and inform vaccine and infectious disease research.
• Autoimmunity and B-cell malignancies: Analyzes somatic hypermutation patterns to investigate roles of selection in autoimmunity and B-cell cancers.
• Pre-immune repertoire diversification: Studies diversification of pre-immune repertoires across species by quantifying selection on immunoglobulin sequences.

Methodology:

Performs IMGT alignment for V(D)J assignment, analyzes somatic mutation patterns using Bayesian estimation (BASELINe), and integrates a Focused binomial test plus Z-score-based statistics to detect and quantify selection.