Identification of Subject-Specific Immunoglobulin Alleles From Expressed Repertoire Sequencing Data

Frontiers in Immunology
Daniel Gadala-MariaSteven H Kleinstein

Abstract

The adaptive immune receptor repertoire (AIRR) contains information on an individuals' immune past, present and potential in the form of the evolving sequences that encode the B cell receptor (BCR) repertoire. AIRR sequencing (AIRR-seq) studies rely on databases of known BCR germline variable (V), diversity (D), and joining (J) genes to detect somatic mutations in AIRR-seq data via comparison to the best-aligning database alleles. However, it has been shown that these databases are far from complete, leading to systematic misidentification of mutated positions in subsets of sample sequences. We previously presented TIgGER, a computational method to identify subject-specific V gene genotypes, including the presence of novel V gene alleles, directly from AIRR-seq data. However, the original algorithm was unable to detect alleles that differed by more than 5 single nucleotide polymorphisms (SNPs) from a database allele. Here we present and apply an improved version of the TIgGER algorithm which can detect alleles that differ by any number of SNPs from the nearest database allele, and can construct subject-specific genotypes with minimal prior information. TIgGER predictions are validated both computationally (using a leave-one-out...Continue Reading

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Citations

Jun 8, 2019·Bioinformatics·Ayelet PeresGur Yaari
Aug 24, 2019·Immunology and Cell Biology·Corey T WatsonAndrew M Collins
May 5, 2020·Nucleic Acids Research·Ivana MikocziovaLudvig M Sollid
May 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hayden N BrochuXinxia Peng
Oct 12, 2019·Nucleic Acids Research·Aviv OmerGur Yaari
Nov 15, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julian Q Zhou, Steven H Kleinstein
Sep 10, 2020·IScience·Lucia CsepregiSai T Reddy
Jan 1, 2021·Frontiers in Immunology·Menno C van ZelmPablo Engel
May 19, 2021·Nature Methods·Kerui PengSerghei Mangul
Jun 28, 2021·Genes and Immunity·Ivana MikocziovaLudvig M Sollid
Nov 25, 2021·Genome Research·Andrei SlabodkinVictor Greiff

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Datasets Mentioned

BETA
MH267285
MH267286
MH332884
MH359407
PRJNA338795

Methods Mentioned

BETA
AIRR-seq
genotyping
PCR
FACS

Software Mentioned

Align
Immcantation
SHazaM
SeqMan Pro (
pRESTO
IgBlast
QUEST
DNASTAR
iHMMune
VDJPipe

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