huARdb: human Antigen Receptor database for interactive clonotype-transcriptome analysis at the single-cell level

Abstract

T-cell receptors (TCRs) and B-cell receptors (BCRs) are critical in recognizing antigens and activating the adaptive immune response. Stochastic V(D)J recombination generates massive TCR/BCR repertoire diversity. Single-cell immune profiling with transcriptome analysis allows the high-throughput study of individual TCR/BCR clonotypes and functions under both normal and pathological settings. However, a comprehensive database linking these data is not yet readily available. Here, we present the human Antigen Receptor database (huARdb), a large-scale human single-cell immune profiling database that contains 444 794 high confidence T or B cells (hcT/B cells) with full-length TCR/BCR sequence and transcriptomes from 215 datasets. All datasets were processed in a uniform workflow, including sequence alignment, cell subtype prediction, unsupervised cell clustering, and clonotype definition. We also developed a multi-functional and user-friendly web interface that provides interactive visualization modules for biologists to analyze the transcriptome and TCR/BCR features at the single-cell level. HuARdb is freely available at https://huarc.net/database with functions for data querying, browsing, downloading, and depositing. In conclusion, huARdb is a comprehensive and multi-perspective atlas for human antigen receptors.

The 2022Nucleic Acids Researchdatabase issue and the online molecular biology database collection

“…This allows experimental data on variant pathogenicity obtained from model organisms to help interpret the consequences of human variants. Molecules of the immune system are the focus of both the venerable IMGT ® databases which contributes an update ( 85 ), and the new human Antigen Receptor database (huARdb ( 86 )) which exploits new single-cell immune profiling and transcriptomics to reveal individual clonotypes of T-cell and B-cell receptors (TCRs and BCRs). Notably, huARdb offers stable URLs for results of analyses of user data at the site to facilitate interactive data sharing.…”

Immune repertoire profiling for disease pathobiology

“…Further repertoire analyses such as clonotype identification (i.e., the classification of the CDR3 sequences) and diversity analysis are performed to interpret the repertoire compositions, and, specifically for the BCR/Ig repertories, SHM profiling and phylogenetic inference analysis are also performed to acquire global views of the affinity maturation processes of BCR/Ig clones. Useful public databases have been constructed for repertoire sequencing data, 28 , 29 , 30 , 31 , 32 which include global BCR/TCR repertoire data sets of humans and mice, some containing TCR repertoires combined with information on defined antigens. Information on the publicly shared clonotypes (CDR3 sequences) of the immune repertoires can help obtain the baseline compositions of the immune repertoires in the general populations and identify disease‐specific repertoires from originally obtained NGS data sets in each laboratory.…”

“…Phylogenetic inference for BCR [24] TRUST4 TCR/BCR reconstruction from bulk and single-cell RNA-seq data [16] BASIC TCR/BCR reconstruction from single-cell RNA-seq data [25] TraCeR/BraCeR [26] Public data set of repertoire data iReceptor bulk BCR/TCR repertoire sequence data (human and mouse) [28] (http://ireceptor.irmacs.sfu.ca/) cAB-rep bulk BCR repertoire sequence data (human) [29] (https://cab-rep.c2b2.columbia.edu) TCR3d TCR repertoire sequence with experimentaly determined 3D structure [30] (https://tcr3d.ibbr.umd.edu) huARdb single cell TCR/BCR repertoire data (human) [31] (https://huarc.net/database) VDJdb curated database of TCR repertoires with antigen specificities [32] (https://vdjdb.cdr3.net/)…”

Advances in antibody discovery from human BCR repertoires

“…IMGT/3Dstructure-DB contains 8,437 entries as of 3 June 2022. • huARdb ( Wu et al, 2022 ) is a versatile and user-friendly web interface consisting of data from 444,794 high confidence T or B cells with full-length TCR/BCR sequences and transcriptomes from 215 datasets, which have been subjected to a uniform workflow. • PIRD ( Zhang et al, 2020 ) is a multi-species BCR dataset that contains 5 main information modules, including project information, sample information, raw sequencing data, annotated TCR or BCR repertoires, and a database of TCRs and BCRs targeting known antigens (TBAbd).…”

“…• huARdb ( Wu et al, 2022 ) is a versatile and user-friendly web interface consisting of data from 444,794 high confidence T or B cells with full-length TCR/BCR sequences and transcriptomes from 215 datasets, which have been subjected to a uniform workflow.…”