MiXCR: software for comprehensive adaptive immunity profiling

Bolotin, Dmitriy A.; Poslavsky, S. V.; Mitrophanov, Igor; Shugay, Mikhail; Mamedov, Ilgar Z.; Putintseva, Ekaterina V.; Chudakov, Dmitriy M.

doi:10.1038/nmeth.3364

Cited by 1,399 publications

(1,239 citation statements)

References 7 publications

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“…1 and Table 1). These mapping percentages are almost comparable with or slightly lower than the results, 91.5, 90.2, 43.9, 91.9, 87.6, 91.1, and 85.3%, obtained using another BCR analysis software, MiXCR [20]. Among the VJC-mapped reads of these IGHs, 98.3% or more of the sequencing reads were confirmed to contain the corresponding C regions ( Fig.…”

Section: Establishment Of Bcr Sequencing Platform Using Illumina Sequsupporting

confidence: 79%

Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy

Kiyotani

Yamaguchi

et al. 2017

J Hum Genet

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B-cell receptors (BCRs) play a critical role in adaptive immunity as they generate highly diverse immunoglobulin repertoires to recognize a wide variety of antigens. To better understand immune responses, it is critically important to establish a quantitative and rapid method to analyze BCR repertoire comprehensively. Here, we developed "Bcrip", a novel approach to characterize BCR repertoire by sequencing millions of BCR cDNA using next-generation sequencer. Using this method and quantitative real-time PCR, we analyzed expression levels and repertoires of BCRs in a total of 17 peanut allergic subjects' peripheral blood samples before and after receiving oral immunotherapy (OIT) or placebo. By our methods, we successfully identified all of variable (V), joining (J), and constant (C) regions, in an average of 79.1% of total reads and 99.6% of these VJC-mapped reads contained the C region corresponding to the isotypes that we aimed to analyze. In the 17 peanut allergic subjects' peripheral blood samples, we observed an oligoclonal enrichment of certain immunoglobulin heavy chain alpha (IGHA) and IGH gamma (IGHG) clones (P = 0.034 and P = 0.027, respectively) in peanut allergic subjects after OIT. This newly developed BCR sequencing and analysis method can be applied to investigate B-cell repertoires in various research areas, including food allergies as well as autoimmune and infectious diseases.

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Section: Establishment Of Bcr Sequencing Platform Using Illumina Sequsupporting

confidence: 79%

Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy

Kiyotani

Yamaguchi

et al. 2017

J Hum Genet

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“…TCRb V, D, and J gene identification; CDR3 sequence extraction; and error corrections in clean reads were performed using miXCR. 36 …”

Section: Data Processing and Analysismentioning

confidence: 99%

High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC

Chen

Zhao

et al. 2016

OncoImmunology

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T lymphocytes, which recognize antigen peptides through specific T cell receptors (TCRs), play an important role in the human adaptive immune response. TCR diversity is closely associated with host immune response and cancer prognosis. Although tumor-infiltrating T lymphocytes have implications for tumor prognosis, few studies have performed a detailed characterization of TCR diversity in both tumor and non-tumor tissues in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Here, we performed high-throughput sequencing of the TCRb chain complementarity determining region 3 (CDR3) of liver-infiltrating T cells from 48 HBV-associated HCC patients. A significantly higher average number of CDR3 aa clonotypes (2259 vs. 1324, p < 0.001), and significantly higher TCR diversity (Gini coefficient, p < 0.001; Simpson index, p < 0.01; Shannon entropy, p < 0.001) were observed in tumor tissues compared with adjacent non-tumor tissues. The ratio of highly expanded clones (HECs) was significantly higher in non-tumor tissues than in tumor tissues when the HEC threshold was defined as 2% or greater (p < 0.05). Our analysis of the median Morisita-Horn index indicated weak TCR repertoire similarity between tumor and matched non-tumor tissues. The median number of shared clones in tumor tissue and matched non-tumor tissue from each patient was 360.5, representing 5.1-15.8% (10.6 § 0.4%) of all clones in each patient. We observed extensive heterogeneity of T lymphocytes in tumors and higher HEC ratios in adjacent non-tumor tissues of HCC patients. The differential T cell repertoires in tumor and non-tumor tissues suggest a distinct T cell immune microenvironment in patients with HBV-associated HCC.

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“…Methods using paired end Illumina sequencing have advanced, however, allowing the capture of longer reads and sequencing of the full variable region and subclass isotyping with certain 2x 300 bp paired end sequencing methods 74. While Illumina offers unprecedented read counts, reconstructing libraries of antibody sequences, which can be in excess of 900 bp if determining subclass, becomes a bioinformatics conundrum, although there are now a large range of tools to facilitate this 75, 76, 77, 78. Paired end data can also be limited in ability to distinguish some somatic variants 79.…”

Section: Repertoire Analysis Approachesmentioning

confidence: 99%

“…Data from Martin et al73 (c) Segregation of IGHV family genes by CDR ‐H3 physicochemical properties. Minkowsky distance clustering by Brepertoire146 on IgM sequences from B cells in early development in 12 different individuals 76. Each sample is a separate individual.…”

Section: Repertoire Analysis Approachesmentioning

confidence: 99%

Immunoglobulin gene analysis as a tool for investigating human immune responses

Dunn-Walters

Townsend

Sinclair

et al. 2018

Immunological Reviews

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SummaryThe human immunoglobulin repertoire is a hugely diverse set of sequences that are formed by processes of gene rearrangement, heavy and light chain gene assortment, class switching and somatic hypermutation. Early B cell development produces diverse IgM and IgD B cell receptors on the B cell surface, resulting in a repertoire that can bind many foreign antigens but which has had self‐reactive B cells removed. Later antigen‐dependent development processes adjust the antigen affinity of the receptor by somatic hypermutation. The effector mechanism of the antibody is also adjusted, by switching the class of the antibody from IgM to one of seven other classes depending on the required function. There are many instances in human biology where positive and negative selection forces can act to shape the immunoglobulin repertoire and therefore repertoire analysis can provide useful information on infection control, vaccination efficacy, autoimmune diseases, and cancer. It can also be used to identify antigen‐specific sequences that may be of use in therapeutics. The juxtaposition of lymphocyte development and numerical evaluation of immune repertoires has resulted in the growth of a new sub‐speciality in immunology where immunologists and computer scientists/physicists collaborate to assess immune repertoires and develop models of immune action.

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MiXCR: software for comprehensive adaptive immunity profiling

Cited by 1,399 publications

References 7 publications

Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy

Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy

High-throughput T cell receptor sequencing reveals distinct repertoires between tumor and adjacent non-tumor tissues in HBV-associated HCC

Immunoglobulin gene analysis as a tool for investigating human immune responses

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