LymphoSeq

LymphoSeq analyzes high-throughput sequencing (HTS) data of T and B cell receptor complementarity determining region 3 (CDR3) sequences to characterize immune repertoires and identify immunoglobulin heavy and light chain (IGH, IGK, IGL) rearrangements from Adaptive Biotechnologies' ImmunoSEQ assay.

Key Features:

• R package: Implements analyses as an R package for processing immune-repertoire sequencing data.
• Data input: Accepts tab-separated value (.tsv) files exported from the ImmunoSEQ analyzer (Adaptive Biotechnologies).
• HTS processing: Processes high-throughput sequencing data of IGH, IGK, IGL loci and CDR3 sequences for repertoire characterization.
• Clonality detection: Identifies clonal IGH and IGK/IGL rearrangements from genomic DNA sequencing data.
• Biallelic rearrangement analysis: Detects disruptions in biallelic IGHD-to-IGHJ diversity-joining (DJ) rearrangement processes.
• Mutagenesis detection: Identifies sequences differing from dominant rearrangements by fewer than 10 nucleotides to indicate ongoing mutagenesis beyond expressed alleles.
• IGHV usage analysis: Analyzes IGHV gene usage to reveal enrichment patterns compared with healthy memory B cells.

Scientific Applications:

• Burkitt lymphoma clonality: Identification of clonal IGH and IGK/IGL rearrangements in Burkitt lymphoma (BL) tumor genomic DNA.
• Biallelic DJ disruption studies: Exploration of disruptions in biallelic IGHD-to-IGHJ DJ rearrangement relevant to BL pathogenesis.
• Somatic mutagenesis mapping: Detection of sequences within <10 nucleotide differences from dominant rearrangements to map targets of ongoing mutagenesis.
• IGHV enrichment analysis: Examination of IGHV gene usage enrichment in BL tumors relative to healthy memory B-cell repertoires.

Methodology:

Leverages HTS data from ImmunoSEQ .tsv exports to identify clonal IGH/IGK/IGL rearrangements, analyze CDR3 sequences and IGHV gene usage, detect sequences differing by fewer than 10 nucleotides from dominant rearrangements, and identify disruptions in biallelic IGHD-to-IGHJ DJ rearrangements.