PIgLET

PIgLET infers germline variable (V) allele genotypes from adaptive immune receptor repertoire sequencing (AIRR-seq) data for T- and B-cell receptor sequences to support immunogenetic analyses.

Key Features:

• Allele Clusters: Clusters ambiguous IGHV alleles that are duplicated or highly similar across genes to reduce allele assignment ambiguity.
• Allele-Based Genotype Inference: Infers presence of specific alleles using thresholds derived from naive population data to call genotypes.
• Robustness to mutation and incomplete coverage: Provides genotype inference effective for highly somatically mutated repertoires and for reads with incomplete V region coverage.
• Alternative V allele naming scheme: Implements an alternative naming scheme for V alleles to reduce alignment and assignment ambiguity.
• Validation with genomic long-read data: Genotype inference has been validated using independent genomic long-read data.
• IUIS nomenclature compatibility: Supports conversion or compatibility with International Union of Immunological Societies (IUIS) V allele nomenclature.

Scientific Applications:

• Immunogenetics: Precise allele identification and genotype determination for T- and B-cell receptor repertoires in immunogenetic studies.
• Analysis of mutated repertoires: Characterization of highly somatically mutated antibody repertoires or datasets with incomplete V region coverage.
• Standardized reporting: Conversion of allele annotations to IUIS nomenclature for standardized comparison and reporting.

Methodology:

Computational methods include clustering of ambiguous IGHV alleles, allele-based genotype inference using thresholds derived from naive population data, an alternative V allele naming scheme, and validation against independent genomic long-read data.