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Crohn's disease (CD) is a chronic relapsing-remitting inflammatory disorder of the gastrointestinal tract that is characterized by altered innate and adaptive immune function. Although massively parallel sequencing studies of the T cell receptor repertoire identified oligoclonal expansion of unique clones, much less is known about the B cell receptor (BCR) repertoire in CD. Here, we present a novel BCR repertoire sequencing data set from ileal biopsies from pediatric patients with CD and controls, and identify CD-specific somatic hypermutation (SHM) patterns, revealed by a machine learning (ML) algorithm trained on BCR repertoire sequences. Moreover, ML classification of a different data set from blood samples of adults with CD versus controls identified that V gene usage, clusters, or mutation frequencies yielded excellent results in classifying the disease (F1 > 90%). In summary, we show that an ML algorithm enables the classification of CD based on unique BCR repertoire features with high accuracy.
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http://dx.doi.org/10.1101/gr.276683.122 | DOI Listing |
Int Immunol
September 2025
Department of Immunology, Graduate School of Medicine, Kyoto University.
B cells play a critical role in tumor immunity, with their presence associated with improved prognosis in various cancers, including endometrial cancer (EC). However, the nature of the B cell response within the tumor microenvironment (TME) remains incompletely understood. In this study, we conducted single-cell analyses of B cells and CD4+ T cells in the TME of EC.
View Article and Find Full Text PDFImmunol Invest
September 2025
Department of Dermatology, Hunan Key Laboratory of Medical Epigenomics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
Objective: To examine whether features of the B cell receptor (BCR) IgG repertoire correlate with disease activity and clinical phenotypes in systemic autoimmune diseases (SAIDs).
Methods: High-throughput sequencing was performed on IgG heavy chain repertoires from 138 patients with SAIDs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma (SSc), and idiopathic inflammatory myopathy (IIM), as well as 36 healthy controls (HC). We analyzed V/D/J gene usage, clonal distribution and diversity, CDR3 length distribution and amino acid usage, and the correlation between specific BCR features and clinical features.
Clin Immunol
August 2025
Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, Harbin 150081, China; Heilongjiang Provincial Key Laboratory of Infection and Immunity, Harbin 150081, China; Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medica
Incomplete immune reconstitution poses a significant challenge for anti-retroviral therapy (ART) in HIV-infected individuals. The role of B cell receptors (BCRs) in immune reconstitution, a critical aspect of the immune system, has not been well elucidated in ART-experienced people. We analyzed the BCR heavy chain repertoire in immune non-responders (INRs) and immune responders (IRs) by next-generation sequencing.
View Article and Find Full Text PDFCell
August 2025
State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen 518083, China; Guangdong Provincial Key Laboratory of Genome Read and Write, BGI Research, Shenzhen 518083, China; Shanxi Medical University-BGI Collaborative Center for Future Medicine, Shanxi Medical University, Ta
Performing total RNA profiling on formalin-fixed, paraffin-embedded (FFPE) samples, the predominant sample conservation method in clinical practice, remains challenging for current spatial transcriptomics techniques. Here, we introduce Stereo-seq V2, which employs random primers to capture and sequence RNAs in situ on FFPE sections and provides single-cell resolution. The random-priming-based strategy offers unbiased transcript capturing and uniform gene body coverage, which increase the sensitivity to marker genes, the efficiency of non-polyadenylation (poly(A)) RNA profiling, and immune repertoire coverage.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Obstetrics and Gynecology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, China.
Background: The immune system is of paramount importance in maintaining human health and defending against pathogens. Among them, the adaptive immune system is a crucial component of the immune system, as it is responsible for generating and modulating the immune repertoire, which is vital for immune responses.
Methods: We conducted a comprehensive analysis of T cell receptor (TCR) and B cell receptor (BCR) clonotypes in the peripheral blood immune repertoire of 20 patients with benign and malignant ovarian tumors.