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Timescale and genetic linkage explain the variable impact of defense systems on horizontal gene transfer 时间尺度和遗传连锁解释了防御系统对水平基因转移的可变影响
IF 7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-10 DOI: 10.1101/gr.279300.124
Yang Liu, Joao Botelho, Jaime Iranzo
Prokaryotes have evolved a wide repertoire of defense systems to prevent invasion by mobile genetic elements (MGE). However, because MGE are vehicles for the exchange of beneficial accessory genes, defense systems could consequently impede rapid adaptation in microbial populations. Here, we study how defense systems impact horizontal gene transfer (HGT) in the short and long terms. By combining comparative genomics and phylogeny-aware statistical methods, we quantified the association between the presence of 7 widespread defense systems and the abundance of MGE in the genomes of 196 bacterial and 1 archaeal species. We also calculated the differences in the rates of gene gain and loss between lineages that possess and lack each defense system. Our results show that the impact of defense systems on HGT is highly taxon- and system-dependent, and in most cases not statistically significant. Timescale analysis reveals that defense systems must persist in a lineage for a relatively long time to exert an appreciable negative impact on HGT. In contrast, for shorter evolutionary timescales, frequent co-acquisition of MGE and defense systems results in a net positive association of the latter with HGT. Given the high turnover rates experienced by defense systems, we propose that the inhibitory effect of most defense systems on HGT is masked by their strong linkage with MGE. These findings help explain the contradictory conclusions of previous research by pointing at mobility and within-host retention times as key factors that determine the impact of defense systems on genome plasticity.
原核生物已经进化出广泛的防御系统来防止移动遗传元件(MGE)的入侵。然而,由于MGE是交换有益附属基因的载体,防御系统可能因此阻碍微生物种群的快速适应。在这里,我们研究防御系统如何影响水平基因转移(HGT)在短期和长期。通过比较基因组学和系统发育意识统计方法的结合,我们量化了196种细菌和1种古细菌基因组中7种广泛存在的防御系统与MGE丰度之间的关系。我们还计算了拥有和缺乏每种防御系统的世系之间基因获得和丢失率的差异。研究结果表明,防御系统对HGT的影响是高度依赖于分类群和系统的,在大多数情况下不具有统计学意义。时间尺度分析表明,防御系统必须在一个谱系中持续相对较长的时间才能对HGT产生明显的负面影响。相比之下,对于较短的进化时间尺度,MGE和防御系统的频繁共同获取导致后者与HGT的净正相关。鉴于防御系统的高流失率,我们认为大多数防御系统对HGT的抑制作用被它们与MGE的强联系所掩盖。这些发现有助于解释先前研究的矛盾结论,指出流动性和宿主内保留时间是决定防御系统对基因组可塑性影响的关键因素。
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引用次数: 0
Hierarchical architecture of neo-sex chromosomes and accelerated adaptive evolution in tortricid moths 圆蛾新性染色体的层次结构与加速适应进化
IF 7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-06 DOI: 10.1101/gr.279569.124
Fangyuan Yang, Li-Jun Cao, Petr Nguyen, Zhong-Zheng Ma, Jin-Cui Chen, Wei Song, Shu-Jun Wei
Sex chromosomes can expand through fusion with autosomes, thereby acquiring unique evolutionary patterns. In butterflies and moths (Lepidoptera), these sex chromosome–autosome (SA) fusions occur relatively frequently, suggesting possible evolutionary advantages. Here, we investigated how SA fusion affects chromosome features and molecular evolution in leafroller moths (Lepidoptera: Tortricidae). Phylogenomic analysis showed that Tortricidae diverged ∼124 million years ago, accompanied by an SA fusion between the Merian elements M(20 + 17) and MZ. In contrast to partial autosomal fusions, the fused neo-Z Chromosome developed a hierarchical architecture, in which the three elements exhibit heterogeneous sequence features and evolutionary patterns. Specifically, the M17 part had a distinct base composition and chromatin domains. Unlike M20 and MZ, M17 was expressed at the same levels as autosomes in both sexes, compensating for the lost gene dosage in females. Concurrently, the SA fusion drove M17 as an evolutionary hotspot, accelerating the evolution of several genes related to ecological adaptation (e.g., ABCCs) and facilitating the divergence of closely related species, whereas the undercompensated M20 did not show such an effect. Thus, accelerated evolution under a novel pattern of dosage compensation may have favored the adaptive radiation of this group. This study demonstrates the association between a karyotype variant and adaptive evolution and explains the recurrent SA fusion in the Lepidoptera.
性染色体可以通过与常染色体融合而扩展,从而获得独特的进化模式。在蝴蝶和飞蛾(鳞翅目)中,这些性染色体-常染色体(SA)融合相对频繁地发生,表明可能具有进化优势。本文研究了SA融合对叶蛾染色体特征和分子进化的影响。系统基因组学分析表明,Tortricidae在大约1.24亿年前开始分化,并伴随着Merian元素M(20 + 17)和MZ之间的SA融合。与部分常染色体融合相比,融合的新z染色体形成了一个层次结构,其中三个元素表现出不同的序列特征和进化模式。具体来说,M17部分具有不同的碱基组成和染色质结构域。与M20和MZ不同,M17在两性中与常染色体的表达水平相同,弥补了雌性中丢失的基因剂量。同时,SA融合使M17成为进化热点,加速了与生态适应相关的几个基因(如abcc)的进化,促进了近亲物种的分化,而补偿不足的M20则没有表现出这种作用。因此,在一种新的剂量补偿模式下的加速进化可能有利于这一群体的适应性辐射。本研究证明了核型变异与适应性进化之间的联系,并解释了鳞翅目中反复发生的SA融合。
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引用次数: 0
Fusion, fission, and scrambling of the bilaterian genome in Bryozoa 苔藓虫中双边基因组的融合、裂变和混乱
IF 7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-06 DOI: 10.1101/gr.279636.124
Thomas D. Lewin, Isabel Jiah-Yih Liao, Mu-En Chen, John D.D. Bishop, Peter W.H. Holland, Yi-Jyun Luo
Groups of orthologous genes are commonly found together on the same chromosome over vast evolutionary distances. This extensive physical gene linkage, known as macrosynteny, is seen between bilaterian phyla as divergent as Chordata, Echinodermata, Mollusca, and Nemertea. Here, we report a unique pattern of genome evolution in Bryozoa, an understudied phylum of colonial invertebrates. Using comparative genomics, we reconstruct the chromosomal evolutionary history of five bryozoans. Multiple ancient chromosome fusions followed by gene mixing led to the near-complete loss of bilaterian linkage groups in the ancestor of extant bryozoans. A second wave of rearrangements, including chromosome fission, then occurred independently in two bryozoan classes, further scrambling bryozoan genomes. We also discover at least five derived chromosomal fusion events shared between bryozoans and brachiopods, supporting the traditional but highly debated Lophophorata hypothesis and suggesting macrosynteny to be a potentially powerful source of phylogenetic information. Finally, we show that genome rearrangements led to the dispersion of genes from bryozoan Hox clusters onto multiple chromosomes. Our findings demonstrate that the canonical bilaterian genome structure has been lost across all studied representatives of an entire phylum, and reveal that linkage group fission can occur very frequently in specific lineages.
在遥远的进化距离上,同源基因群通常在同一染色体上被发现。这种广泛的物理基因连锁,被称为大同步,在脊索动物、棘皮动物、软体动物和内默特亚动物等不同的双边门之间可见。在这里,我们报告了苔藓虫基因组进化的独特模式,这是一种未被充分研究的殖民地无脊椎动物门。利用比较基因组学,我们重建了5种苔藓虫的染色体进化史。多个古代染色体融合之后的基因混合导致现存苔藓虫祖先的双边连锁群几乎完全消失。第二波重排,包括染色体裂变,随后在两类苔藓虫中独立发生,进一步扰乱了苔藓虫的基因组。我们还发现在苔藓虫和腕足动物之间至少有5个衍生的染色体融合事件,这支持了传统的但备受争议的Lophophorata假说,并表明macrosynteny是一个潜在的强大的系统发育信息来源。最后,我们表明,基因组重排导致基因分散从苔藓虫Hox簇到多个染色体。我们的研究结果表明,在整个门的所有研究代表中,典型的双侧基因组结构已经丢失,并揭示了连锁群裂变在特定谱系中可能非常频繁地发生。
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引用次数: 0
UV damage and repair maps in Drosophila reveal the impact of domain-specific changes in nucleosome repeat length on repair efficiency 果蝇的紫外线损伤和修复图谱揭示了核小体重复长度的区域特异性变化对修复效率的影响
IF 7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-06 DOI: 10.1101/gr.279605.124
Benjamin Morledge-Hampton, Kathiresan Selvam, Manish Chauhan, Alan Goodman, John J. Wyrick
Cyclobutane pyrimidine dimers (CPDs) are formed in DNA following exposure to ultraviolet (UV) light and are mutagenic unless repaired by nucleotide excision repair (NER). It is known that CPD repair rates vary in different genome regions due to transcription-coupled NER and differences in chromatin accessibility; however, the impact of regional chromatin organization on CPD formation remains unclear. Furthermore, nucleosomes are known to modulate UV damage and repair activity, but how these damage and repair patterns are affected by the overarching chromatin domains in which these nucleosomes are located is not understood. Here, we generated a new CPD damage map in Drosophila S2 cells using CPD-seq and analyzed it alongside existing excision repair-sequencing (XR-seq) data to compare CPD damage formation and repair rates across five previously established chromatin types in Drosophila. This analysis revealed that repair activity varied substantially across different chromatin types, while CPD formation was relatively unaffected. Moreover, we observed distinct patterns of repair activity in nucleosomes located in different chromatin types, which we show is due to domain-specific differences in nucleosome repeat length (NRL). These findings indicate that NRL is altered in different chromatin types in Drosophila and that changes in NRL modulate the repair of UV lesions.
环丁烷嘧啶二聚体(CPDs)在DNA暴露于紫外线(UV)光后形成,除非通过核苷酸切除修复(NER)修复,否则具有诱变性。众所周知,由于转录偶联NER和染色质可及性的差异,CPD修复率在不同的基因组区域有所不同;然而,区域染色质组织对CPD形成的影响尚不清楚。此外,已知核小体调节紫外线损伤和修复活性,但这些损伤和修复模式如何受到核小体所在的总体染色质结构域的影响尚不清楚。在这里,我们使用CPD-seq在果蝇S2细胞中生成了一个新的CPD损伤图,并将其与现有的切除修复测序(XR-seq)数据一起分析,以比较果蝇中五种先前建立的染色质类型的CPD损伤形成和修复率。该分析显示,修复活性在不同的染色质类型之间存在很大差异,而CPD的形成相对不受影响。此外,我们在不同染色质类型的核小体中观察到不同的修复活性模式,我们认为这是由于核小体重复长度(NRL)的区域特异性差异。这些发现表明,NRL在果蝇的不同染色质类型中发生改变,NRL的变化调节了紫外线损伤的修复。
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引用次数: 0
Identification of the shortest species-specific oligonucleotide sequences 物种特异性最短寡核苷酸序列的鉴定
IF 7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-02 DOI: 10.1101/gr.280070.124
Ioannis Mouratidis, Maxwell Konnaris, Nikol Chantzi, Candace S.Y Chan, Michail Patsakis, Kimonas Provatas, Austin Montgomery, Fotis A. Baltoumas, Congzhou M. Sha, Manvita Mareboina, Georgios A. Pavlopoulos, Dionysios V. Chartoumpekis, Ilias Georgakopoulos-Soares
Despite the exponential increase in sequencing information driven by massively parallel DNA sequencing technologies, universal and succinct genomic fingerprints for each organism are still missing. Identifying the shortest species-specific nucleic sequences offers insights into species evolution and holds potential practical applications in agriculture, wildlife conservation, and healthcare. We propose a new method for sequence analysis termed nucleic "quasi-primes", the shortest occurring sequences in each of 45,785 organismal reference genomes, present in one genome and absent from every other examined genome. In the human genome, we find that the genomic loci of nucleic quasi-primes are most enriched for genes associated with brain development and cognitive function. In a single-cell case study focusing on the human primary motor cortex, nucleic quasi-prime genes account for a significantly larger proportion of the variation based on average gene expression. Non-neuronal cell types, including astrocytes, endothelial cells, microglia perivascular-macrophages, oligodendrocytes, and vascular and leptomeningeal cells, exhibited significant activation of quasi-prime containing gene associations related to cancer, while simultaneously suppressing quasi-prime containing genes were associated with cognitive, mental, and developmental disorders. We also show that human disease-causing variants, eQTLs, mQTLs and sQTLs are 4.43-fold, 4.34-fold, 4.29-fold and 4.21-fold enriched at human quasi-prime loci, respectively. These findings indicate that nucleic quasi-primes are genomic loci linked to the evolution of species-specific traits and in humans they provide insights in the development of cognitive traits and human diseases, including neurodevelopmental disorders.
尽管在大规模并行DNA测序技术的推动下,测序信息呈指数级增长,但每种生物的通用和简洁的基因组指纹仍然缺失。确定最短的物种特异性核酸序列提供了对物种进化的见解,并在农业、野生动物保护和医疗保健方面具有潜在的实际应用。我们提出了一种新的序列分析方法,称为核酸“准引物”,即在45,785个生物体参考基因组中出现的最短序列,存在于一个基因组中,而不存在于其他所有被检查的基因组中。在人类基因组中,我们发现与大脑发育和认知功能相关的基因在核酸准引物的基因组位点中最为丰富。在一项针对人类初级运动皮层的单细胞案例研究中,基于平均基因表达的变异中,核准主要基因占比明显更大。非神经元细胞类型,包括星形胶质细胞、内皮细胞、小胶质血管周围巨噬细胞、少突胶质细胞、血管细胞和轻脑膜细胞,显示出与癌症相关的准起始基因的显著激活,同时抑制与认知、精神和发育障碍相关的准起始基因。我们还发现,人类致病变异、eqtl、mqtl和sqtl分别在人类准prime位点富集4.43倍、4.34倍、4.29倍和4.21倍。这些发现表明,核准引物是与物种特异性特征进化相关的基因组位点,在人类中,它们为认知特征和人类疾病(包括神经发育障碍)的发展提供了见解。
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引用次数: 0
Probing the eukaryotic microbes of ruminants with a deep-learning classifier and comprehensive protein databases 利用深度学习分类器和综合蛋白质数据库探测反刍动物真核微生物
IF 7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-27 DOI: 10.1101/gr.279825.124
Ming Yan, Thea Os Andersen, Phil B. Pope, Zhongtang Yu
Metagenomics, particularly genome-resolved metagenomics, has significantly deepened our understanding of microbes, illuminating their taxonomic and functional diversity and roles in ecology, physiology, and evolution. However, eukaryotic populations within various microbiomes, including those in the mammalian gastrointestinal (GI) tract, remain relatively underexplored in metagenomic studies due to the lack of comprehensive reference genome databases and robust bioinformatics tools. The GI tract of ruminants, particularly the rumen, contains a high eukaryotic biomass although a relatively low diversity of ciliates and fungi, which significantly impacts feed digestion, methane emissions, and rumen microbial ecology. In the present study, we developed GutEuk, a bioinformatics tool that improves upon the currently available Tiara and EukRep in accurately identifying eukaryotic sequences from metagenomes. GutEuk is optimized for high precision across different sequence lengths. It can also distinguish fungal and protozoal sequences, further elucidating their unique ecological, physiological, and nutritional impacts. GutEuk was shown to facilitate comprehensive analyses of protozoa and fungi within more than one thousand rumen metagenomes, revealing a greater genomic diversity among protozoa than previously documented. We further curated several ruminant eukaryotic protein databases, significantly enhancing our ability to distinguish the functional roles of ruminant fungi and protozoa from those of prokaryotes. Overall, the newly developed package GutEuk and its associated databases create new opportunities for in-depth study of GI tract eukaryotes.
宏基因组学,特别是基因组解析宏基因组学,极大地加深了我们对微生物的认识,阐明了它们的分类和功能多样性以及在生态学、生理学和进化中的作用。然而,由于缺乏全面的参考基因组数据库和强大的生物信息学工具,各种微生物组中的真核生物群体,包括哺乳动物胃肠道中的微生物群,在宏基因组研究中仍然相对不足。反刍动物的胃肠道,尤其是瘤胃,虽然纤毛虫和真菌的多样性相对较低,但真核生物的生物量很高,这对饲料消化、甲烷排放和瘤胃微生物生态有重要影响。在本研究中,我们开发了GutEuk,这是一种生物信息学工具,改进了目前可用的Tiara和EukRep,可以准确地从元基因组中识别真核生物序列。GutEuk针对不同序列长度的高精度进行了优化。它还可以区分真菌和原生动物序列,进一步阐明其独特的生态,生理和营养作用。GutEuk被证明可以促进对1000多个瘤胃宏基因组中原生动物和真菌的综合分析,揭示了原生动物之间比以前记录的更大的基因组多样性。我们进一步整理了几个反刍动物真核蛋白数据库,大大提高了我们区分反刍真菌和原生动物与原核生物的功能作用的能力。总之,新开发的软件包GutEuk及其相关数据库为深入研究胃肠道真核生物创造了新的机会。
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引用次数: 0
Combining DNA and protein alignments to improve genome annotation with LiftOn 结合DNA和蛋白质比对改进LiftOn基因组注释
IF 7 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-27 DOI: 10.1101/gr.279620.124
Kuan-Hao Chao, Jakob M Heinz, Celine Hoh, Alan Mao, Alaina Shumate, Mihaela Pertea, Steven Salzberg
As the number and variety of assembled genomes continues to grow, the number of annotated genomes is falling behind, particularly for eukaryotes. DNA-based mapping tools help to address this challenge, but they are only able to transfer annotation between closely-related species. Here we introduce LiftOn, a homology-based software tool that integrates DNA and protein alignments to enhance the accuracy of genome-scale annotation and to allow mapping between relatively distant species. LiftOn's protein-centric algorithm considers both types of alignments, chooses optimal open reading frames, resolves overlapping gene loci, and finds additional gene copies where they exist. LiftOn can reliably transfer annotation between genomes representing members of the same species, as we demonstrate on human, mouse, honeybee, rice, and Arabidopsis thaliana. It can further map annotation effectively across species pairs as far apart as mouse and rat or Drosophila melanogaster and D. erecta.
随着组装基因组的数量和种类不断增加,注释基因组的数量正在落后,特别是对于真核生物。基于dna的制图工具有助于解决这一挑战,但它们只能在密切相关的物种之间传递注释。在这里,我们介绍LiftOn,一个基于同源性的软件工具,集成了DNA和蛋白质比对,以提高基因组尺度注释的准确性,并允许在相对遥远的物种之间进行定位。LiftOn的以蛋白质为中心的算法考虑了这两种类型的比对,选择了最佳的开放阅读框,解决了重叠的基因位点,并在它们存在的地方找到了额外的基因拷贝。LiftOn可以可靠地在代表同一物种成员的基因组之间传递注释,正如我们在人类、小鼠、蜜蜂、水稻和拟南芥上所证明的那样。它可以进一步有效地在物种对之间进行标注,最远可以是小鼠和大鼠,也可以是果蝇和D. erecta。
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引用次数: 0
Inferring ancestry with the hierarchical soft clustering approach tangleGen. 用分层软聚类法 tangleGen 推断祖先。
IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-23 DOI: 10.1101/gr.279399.124
Klara Elisabeth Burger, Solveig Klepper, Ulrike von Luxburg, Franz Baumdicker

Understanding the genetic ancestry of populations is central to numerous scientific and societal fields. It contributes to a better understanding of human evolutionary history, advances personalized medicine, aids in forensic identification, and allows individuals to connect to their genealogical roots. Existing methods, such as ADMIXTURE, have significantly improved our ability to infer ancestries. However, these methods typically work with a fixed number of independent ancestral populations. As a result, they provide insight into genetic admixture, but do not include a hierarchical interpretation. In particular, the intricate ancestral population structures remain difficult to unravel. Alternative methods with a consistent inheritance structure, such as hierarchical clustering, may offer benefits in terms of interpreting the inferred ancestries. Here, we present tangleGen, a soft clustering tool that transfers the hierarchical machine learning framework Tangles, which leverages graph theoretical concepts, to the field of population genetics. The hierarchical perspective of tangleGen on the composition and structure of populations improves the interpretability of the inferred ancestral relationships. Moreover, tangleGen adds a new layer of explainability, as it allows identifying the single-nucleotide polymorphisms that are responsible for the clustering structure. We demonstrate the capabilities and benefits of tangleGen for the inference of ancestral relationships, using both simulated data and data from the 1000 Genomes Project.

了解人口的遗传祖先对许多科学和社会领域都至关重要。它有助于更好地了解人类进化史,促进个性化医疗,帮助法医鉴定,并让个人与自己的家谱根源建立联系。ADMIXTURE 等现有方法大大提高了我们推断祖先的能力。然而,这些方法通常只适用于固定数量的独立祖先人群。因此,这些方法虽然能让我们深入了解基因混杂的情况,但并不包括层次解释。特别是,错综复杂的祖先种群结构仍然难以解开。具有一致遗传结构的替代方法,如分层聚类,可能会在解释推断的祖先方面带来好处。在这里,我们介绍一种软聚类工具 tangleGen,它将利用图论概念的分层机器学习框架 Tangles 移植到了群体遗传学领域。tangleGen 从分层的角度看待种群的组成和结构,提高了推断祖先关系的可解释性。此外,tangleGen 还增加了一层新的可解释性,因为它可以确定造成聚类结构的 SNPs。我们利用模拟数据和来自 1000 基因组计划的数据展示了 tangleGen 在推断祖先关系方面的能力和优势。
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引用次数: 0
Reviewer Index, Volume 34, 2024. 审稿人索引,第34卷,2024年。
IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-23
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引用次数: 0
Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR. 利用 MiXCR 从免疫谱系测序数据中进行超灵敏等位基因推断。
IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-23 DOI: 10.1101/gr.278775.123
Artem Mikelov, George Nefediev, Alexander Tashkeev, Oscar L Rodriguez, Diego Aguilar Ortmans, Valeriia Skatova, Mark Izraelson, Alexey N Davydov, Stanislav Poslavsky, Souad Rahmouni, Corey T Watson, Dmitriy Chudakov, Scott D Boyd, Dmitry Bolotin

Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci. Here, we present a novel algorithm for extrasensitive and specific variable (V) and joining (J) gene allele inference, allowing the reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput novel allele discovery from a wide variety of existing data sets. The developed algorithm is a part of the MiXCR software. We demonstrate the accuracy of this approach using AIRR-seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) AIRR-seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRA and TRB) AIRR-seq data set, representing 134 individuals. This allowed us to assess the genetic diversity within the IGH, TRA, and TRB loci in different populations and to establish a database of alleles of V and J genes inferred from AIRR-seq data and their population frequencies with free public access through VDJ.online database.

适应性免疫受体基因座中的等位基因变异性对病原体和疫苗的免疫反应至关重要,而适应性免疫受体基因座中含有编码 B 细胞和 T 细胞受体(BCR/TCR)的基因片段。适应性免疫受体复合物测序(AIRR-seq)已在免疫学研究中得到广泛应用,使其成为有关免疫球蛋白(IG)和T细胞受体(TR)基因座等位基因多样性的最便捷信息来源。在这里,我们提出了一种用于超灵敏和特异性可变(V)和连接(J)基因等位基因推断的新算法,允许重建单个高质量基因片段库。该方法可用于从外周血淋巴细胞 BCR 和 TCR 重排测序数据(包括高突变同型切换 BCR 序列)中推断等位基因变异,从而实现从各种现有数据集中高通量发现新型等位基因。开发的算法是 MiXCR 软件的一部分。我们使用 AIRR-seq 与长线程基因组测序数据配对,证明了这种方法的准确性,并将其与广泛使用的算法 TIgGER 进行了比较。我们将该算法应用于来自不同祖先群体的 450 名供体的大量 IG 重链(IGH)AIRR-seq 数据集,以及已报道的代表 134 个个体的最大全长 TCR alpha 和 beta 链(TRA; TRB)AIRR-seq 数据集。这使我们能够评估不同人群中 IGH、TRA 和 TRB 位点的遗传多样性,并建立了一个数据库,其中包含从 AIRR-seq 数据中推断出的 V 和 J 基因等位基因及其人群频率,公众可通过在线数据库免费访问。
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引用次数: 0
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