Inference of B cell clonal families using heavy/light chain pairing information.
Inference of B cell clonal families using heavy/light chain pairing information.
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DOI：
10.1371/journal.pcbi.1010723
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发表时间：
2022-11
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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下一代B细胞受体(BCR)谱系的测序已经成为理解抗体介导的免疫反应的普遍工具：现在通常有大量的序列数据编码BCR的重链和轻链亚基。然而，直到最近发展了保存重/轻链配对信息的高通量方法之前，这些样本没有关于哪个重链序列与哪个轻链序列配对的明确信息。分析这种BCR谱系样本的第一步之一是将序列分组到克隆相关的家族中，其中每个家族都源于一个单一的重排事件。已经开发了许多实现这一点的方法，然而，到目前为止，还没有一种方法充分利用新获得的配对信息。这些信息可以显著提高集群性能，尤其是对于轻链。传统上，轻链一直是克隆家族推理的挑战，因为它的多样性较低，从而导致大量无法区分的幼稚重排的非克隆家族。在这里，我们提出了一种方法，将这种配对信息合并到聚类过程中，以便更准确地将数据划分为克隆相关的家族。我们还展示了两种修复不完美配对信息的方法，这可能允许简化样本准备和增加测序深度。最后，我们描述了对PARS软件包的其他几个改进。抗体是获得性免疫反应的一部分，对接种疫苗和感染所获得的免疫力至关重要。B细胞受体(BCR)谱系的下一代测序提供了产生抗体的DNA序列的广泛和高度信息量的观点。然而，直到最近，这些测序数据还不能将组成功能性抗体的两个区域(来自不同的染色体)配对在一起。在这篇文章中，我们提出了几种方法来改进对新配对数据的分析，这些配对数据确实将完整抗体的序列数据配对在一起。我们首先展示了一种更好地将来自同一祖先细胞的序列组合在一起的方法，解决了一个称为“克隆家族推断”的问题。然后，我们展示了两种方法，它们可以纠正数据识别中的各种不完美之处，即哪些序列配对在一起形成完整的抗体，这两种方法结合在一起可能会大大简化实验方法。
Next generation sequencing of B cell receptor (BCR) repertoires has become a ubiquitous tool for understanding the antibody-mediated immune response: it is now common to have large volumes of sequence data coding for both the heavy and light chain subunits of the BCR. However, until the recent development of high throughput methods of preserving heavy/light chain pairing information, these samples contained no explicit information on which heavy chain sequence pairs with which light chain sequence. One of the first steps in analyzing such BCR repertoire samples is grouping sequences into clonally related families, where each stems from a single rearrangement event. Many methods of accomplishing this have been developed, however, none so far has taken full advantage of the newly-available pairing information. This information can dramatically improve clustering performance, especially for the light chain. The light chain has traditionally been challenging for clonal family inference because of its low diversity and consequent abundance of non-clonal families with indistinguishable naive rearrangements. Here we present a method of incorporating this pairing information into the clustering process in order to arrive at a more accurate partition of the data into clonally related families. We also demonstrate two methods of fixing imperfect pairing information, which may allow for simplified sample preparation and increased sequencing depth. Finally, we describe several other improvements to the partis software package. Antibodies form part of the adaptive immune response, and are critical to immunity acquired by both vaccination and infection. Next generation sequencing of the B cell receptor (BCR) repertoire provides a broad and highly informative view of the DNA sequences from which antibodies arise. Until recently, however, this sequencing data was not able to pair together the two domains (from separate chromosomes) that make up a functional antibody. In this paper we present several methods to improve analysis of the new paired data that does pair together sequence data for complete antibodies. We first show a method that better groups together sequences stemming from the same ancestral cell, solving a problem called “clonal family inference.” We then show two methods that can correct for various imperfections in the data’s identification of which sequences pair together to form complete antibodies, which together may allow for significantly simplified experimental methods.
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DOI：
10.4049/jimmunol.2000583
发表时间：
2020-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Alsoussi WB;Turner JS;Case JB;Zhao H;Schmitz AJ;Zhou JQ;Chen RE;Lei T;Rizk AA;McIntire KM;Winkler ES;Fox JM;Kafai NM;Thackray LB;Hassan AO;Amanat F;Krammer F;Watson CT;Kleinstein SH;Fremont DH;Diamond MS;Ellebedy AH
通讯作者：
Ellebedy AH
影响因子：
17.1
作者：
Howie, Bryan;Sherwood, Anna M.;Robins, Harlan S.
通讯作者：
Robins, Harlan S.
影响因子：
5.4
作者：
Doepker, Laura E.;Simonich, Cassandra A.;Overbaugh, Julie M.
通讯作者：
Overbaugh, Julie M.
影响因子：
6.6
作者：
Hagen O;Stadler T
通讯作者：
Stadler T
DOI：
10.4049/jimmunol.2100135
发表时间：
2021-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hoehn KB;Ramanathan P;Unterman A;Sumida TS;Asashima H;Hafler DA;Kaminski N;Dela Cruz CS;Sealfon SC;Bukreyev A;Kleinstein SH
通讯作者：
Kleinstein SH