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通过多任务深度学习增强适应性免疫受体的序列比对

Enhancing sequence alignment of adaptive immune receptors through multi-task deep learning.

作者信息

Konstantinovsky Thomas, Peres Ayelet, Eisenberg Ran, Polak Pazit, Lindenbaum Ofir, Yaari Gur

机构信息

Department of Bioengineering, Faculty of Engineering, Bar Ilan University, 5290002 Ramat Gan, Israel.

Bar Ilan Institute of Nanotechnology and Advanced Materials, Bar Ilan University, 5290002 Ramat Gan, Israel.

出版信息

Nucleic Acids Res. 2025 Jul 8;53(13). doi: 10.1093/nar/gkaf651.

DOI:10.1093/nar/gkaf651
PMID:40650972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12255302/
Abstract

Sequence alignment of immunoglobulin (Ig) sequences is central to the computational analysis of adaptive immune receptor repertoire sequencing (AIRR-seq) data, impacting adaptive immunity research and antibody engineering. Traditional Ig sequence aligners often struggle to handle the complexities of V(D)J recombination and somatic hypermutation (SHM), resulting in suboptimal allele assignment accuracy and sequence segmentation. We introduce AlignAIR, a novel deep learning-based aligner that leverages advanced simulation approaches and a multi-task learning framework. AlignAIR sets new state-of-the-art results in allele assignment accuracy, productivity assessments, sequence segmentation, and speed. The model's latent space captures SHM characteristics, offering more profound insights into sequence variability. AlignAIR is designed for seamless integration with existing AIRR-seq pipelines and includes a user-friendly web interface and a container image for efficient local processing of millions of sequences. AlignAIR represents a significant advancement in immunogenetics research and antibody engineering, providing a critical resource for analyzing adaptive immune receptor repertoires.

摘要

免疫球蛋白(Ig)序列的比对是适应性免疫受体组库测序(AIRR-seq)数据计算分析的核心,对适应性免疫研究和抗体工程有重要影响。传统的Ig序列比对工具常常难以处理V(D)J重组和体细胞超突变(SHM)的复杂性,导致等位基因分配准确性和序列分割效果欠佳。我们推出了AlignAIR,这是一种基于深度学习的新型比对工具,它利用了先进的模拟方法和多任务学习框架。AlignAIR在等位基因分配准确性、生产力评估、序列分割和速度方面创造了新的最先进成果。该模型的潜在空间捕捉到了SHM特征,能更深入地洞察序列变异性。AlignAIR旨在与现有的AIRR-seq流程无缝集成,包括一个用户友好的网页界面和一个容器镜像,用于对数以百万计的序列进行高效的本地处理。AlignAIR代表了免疫遗传学研究和抗体工程的重大进展,为分析适应性免疫受体组库提供了关键资源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/890b30516aed/gkaf651fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/033e6c57eaa1/gkaf651figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/fe6989690fd3/gkaf651fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/3eb4e01c1bdd/gkaf651fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/1c8e8b85b6c1/gkaf651fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/890b30516aed/gkaf651fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/033e6c57eaa1/gkaf651figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/fe6989690fd3/gkaf651fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/3eb4e01c1bdd/gkaf651fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/1c8e8b85b6c1/gkaf651fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c81/12255302/890b30516aed/gkaf651fig4.jpg

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本文引用的文献

1
Disease diagnostics using machine learning of B cell and T cell receptor sequences.利用B细胞和T细胞受体序列的机器学习进行疾病诊断
Science. 2025 Feb 21;387(6736):eadp2407. doi: 10.1126/science.adp2407.
2
BetaAlign: a deep learning approach for multiple sequence alignment.BetaAlign:一种用于多序列比对的深度学习方法。
Bioinformatics. 2024 Dec 26;41(1). doi: 10.1093/bioinformatics/btaf009.
3
An unbiased comparison of immunoglobulin sequence aligners.免疫球蛋白序列比对工具的无偏比较。
Brief Bioinform. 2024 Sep 23;25(6). doi: 10.1093/bib/bbae556.
4
Detection of disease-specific signatures in B cell repertoires of lymphomas using machine learning.利用机器学习在淋巴瘤 B 细胞受体库中检测疾病特异性标志物。
PLoS Comput Biol. 2024 Jul 2;20(7):e1011570. doi: 10.1371/journal.pcbi.1011570. eCollection 2024 Jul.
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Guidelines for reproducible analysis of adaptive immune receptor repertoire sequencing data.适应性免疫受体测序数据分析可重复性分析指南。
Brief Bioinform. 2024 Mar 27;25(3). doi: 10.1093/bib/bbae221.
6
Self-supervised learning of T cell receptor sequences exposes core properties for T cell membership.基于 TCR 序列的自监督学习揭示了 T 细胞身份的核心特征。
Sci Adv. 2024 Apr 26;10(17):eadk4670. doi: 10.1126/sciadv.adk4670.
7
AIRR-C IG Reference Sets: curated sets of immunoglobulin heavy and light chain germline genes.AIRR-C IG 参考集:经过精心挑选的免疫球蛋白重链和轻链种系基因集。
Front Immunol. 2024 Feb 9;14:1330153. doi: 10.3389/fimmu.2023.1330153. eCollection 2023.
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B cell phylogenetics in the single cell era.单细胞时代的 B 细胞系统发生。
Trends Immunol. 2024 Jan;45(1):62-74. doi: 10.1016/j.it.2023.11.004. Epub 2023 Dec 27.
9
Language model-based B cell receptor sequence embeddings can effectively encode receptor specificity.基于语言模型的 B 细胞受体序列嵌入可以有效地编码受体特异性。
Nucleic Acids Res. 2024 Jan 25;52(2):548-557. doi: 10.1093/nar/gkad1128.
10
DeepAIR: A deep learning framework for effective integration of sequence and 3D structure to enable adaptive immune receptor analysis.DeepAIR:一个深度学习框架,用于有效地整合序列和 3D 结构,以实现适应性免疫受体分析。
Sci Adv. 2023 Aug 9;9(32):eabo5128. doi: 10.1126/sciadv.abo5128.