NAR Human Antigen Receptor Database huARdb was published, realizing the combined analysis of clonotype and transcriptome visualization, reaching the single-cell level

Adaptive immunity is mediated by T cells and B cells, responsible for the recognition and elimination of specific antigens and the formation of long-term immune memory [1,2]
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Both T cells and B cells rely on antigen receptors expressed on their cell surfaces, that is, T cell receptors (TCR) or B cell receptors (BCR) to specifically recognize antigens [3]
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During the maturation of T cells and B cells, random V(D)J gene recombination produces unique TCR/BCR for each cell, forming a highly diverse library of TCRs/BCRs in the human body [4] to cope with the environment Abundant and diverse pathogenic organisms
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Understanding the sequence of TCR/BCR and the corresponding antigenic characteristics is essential for biologists to better understand how the adaptive immune system exerts its effector functions under the stimulation of specific pathogens or specific antigens
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Single-cell immune repertoire analysis combined with single-cell transcriptome analysis enables high-throughput research on the clonotype and function of a single TCR/BCR under normal and pathological conditions
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For example, the single-cell immune repertoire data of samples of ulcerative colitis revealed the clonal evolution of T cells in diseased tissues [5]
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A large number of public single-cell immune repertoire data generated in the past time requires in-depth analysis to reveal more immunological mechanisms
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However, there is currently no method to reuse and unbiased integrated analysis of published single-cell immune repertoire data
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On October 4, 2021, researcher Liu Wanlu and Professor Lu Linrong’s research group from the Joint College of the University of Edinburgh, Zhejiang University published a collaboration entitled huARdb: human Antigen Receptor database for interactive clonotype-transcriptome analysis at the single-cell level in Nucleic Acids Research.
Research papers
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The research established the first human T cell receptor (TCR) and B cell receptor (BCR) database based on single-cell immune profiling by collecting data from the public single-cell immune profiling.
An interactive visualization web tool that includes a variety of transcriptome and immune receptor data analysis tools, enabling biologists to jointly analyze clonotype-transcriptome characteristics in immune repertoire data, as well as joint analysis of gene expression characteristics at the single-cell level and TCR/BCR features
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The huARdb database collected 215 single-cell immune repertoire data
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These data come from 493 different sequencing libraries, 24 different tissues and 12 different disease models (Figure 1)
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The existing database contains 444794 T/B cells and 287060 T/B cell clonotypes (Figure 1)
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The author uses a unified process (genome comparison, T cell and B cell subtype prediction, unsupervised cell clustering, clonotype definition, etc.
) to process the data of each single cell immune repertoire to obtain a single data set.
Cell-level TCR/BCR and transcriptome characteristics (Figure 1)
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The author developed a web page to display the transcriptome-related features and TCR/BCR-related features of each data set in the database
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Users can watch the operation demonstration video (the last video) on the homepage, and analyze the samples of interest through disease, tissue type, cell type index (Figure 2A)
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For a single immune repertoire database data set, users can view various transcriptome characteristics of the data.
For example, the webpage shows the distribution of cells of each subtype on the tSNE graph.
When the user is interested in a certain cell subtype, you can view it on the webpage Select the name of the corresponding cell subtype in the menu to highlight the cell distribution of a specific subtype (Figure 2B)
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At the same time, users can also view other transcriptome characteristics of the data set on the web page, including statistical information of cell subtypes, and the expression patterns of individual genes
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Figure 1: Shows the data summary, construction process and analysis modules of the huARdb database.
Figure 2: Shows the huARdb database homepage and part of the transcriptome analysis tool.
This study developed the first clonotype-transcriptome joint visual analysis method
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Cell clonotypes can be defined by cell TCR/BCR characteristics
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Users can not only view the cell frequency of each clonotype, but also analyze the transcriptome characteristics of the highly amplified clonal cells in the data set.
For example, you can see the distribution information of cell subtypes within each clonotype (Figure 3A)
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At the same time, users can view the TCR/BCR information (such as V(D)J gene usage and coding sequence, etc.
, Figure 3B/D) and transcriptome information (cell subtypes) of each highly amplified cloned cell at the single cell level Information, single gene expression level, etc.
, Figure 3C), and the web page provides information download function
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In addition, users can also analyze the overall transcriptome characteristics of the same clonotype cell, as well as the gene expression characteristics of highly amplified cells of a specific subtype
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Through the human antigen receptor database and interactive visual web analysis tools, the functions of TCR/BCR in different immune environments will be further revealed
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Figure 3: Part of the clonotype-transcriptome analysis module of the huARdb database is shown.
The corresponding authors of the paper are researcher Liu Wanlu and Professor Lu Linrong from the Joint College of the University of Edinburgh, Zhejiang University
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Wu Lize, a doctoral student at Zhejiang University School of Medicine, and Xue Zi, a doctoral student at the Union College of Edinburgh University, Zhejiang University, are the co-first authors of this article
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Assistant researcher Dr.
Xuexiao Jin, postdoctoral fellow Bai Yadan, doctoral student Guo Yixin, research assistant Jin Shaqian, and biomedical undergraduate student Zhang Jinchun participated in this research
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This work was also supported by researcher James Q.
Wang and Wang Chaochen from the Union College of the University of Edinburgh, Zhejiang University, researcher Liu Zuozhu from the Union College of the University of Illinois at Urbana-Champaign, Zhejiang University, and Professor Wang Li from Zhejiang University School of Medicine
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The research group introduced that the main research directions of Liu Wanlu's research group are epigenetics, genomics, bioinformatics, stem cells and regenerative medicine.
Currently, they are committed to studying the apparent regulatory mechanism of transposon and its role in cell fate determination.
The laboratory also focuses on the development of bioinformatics algorithms, databases, and web tools for single-cell data in multi-omics data sets
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Laboratory website: https://labw.
org The main research direction of Lu Linrong's research group is to use molecular biology, cell biology, experimental animal models and biological information to reveal the mechanism of immune regulation
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He is particularly interested in the research of thymic T cell development, CD8+ T cell subsets and new molecules with immunomodulatory functions, and at the same time researches on strategies for immunotherapy of autoimmune diseases and tumors
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Laboratory website: https://person.
zju.
edu.
cn/llr resume delivery (if interested, please send your resume and other materials to): https://jinshuju.
net/f/ZqXwZt or scan the QR code to deliver your resume Original link: https://academic.
oup.
com/nar/advance-article/doi/10.
1093/nar/gkab857/6381136 Platemaker: 11 References 1.
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Qi,Q.
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, Lee,JY, Olshen,RA, Weyand,CM, Boyd,SD and Goronzy,JJ (2014) Diversity and clonal selection in the human T-cell repertoire.
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Corridoni,D.
, Antanaviciute,A.
, Gupta,T.
, Fawkner-Corbett,D.
, Aulicino,A.
, Jagielowicz,M.
, Parikh,K.
, Repapi,E.
, Taylor,S.
, Ishikawa,D.
et al.
(2020) Single-cell atlas of colonic CD8(+) T cells in ulcerative colitis.
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