推断B细胞库多样性背后的过程
Inferring processes underlying B-cell repertoire diversity
摘要：
我们量化的VDJ重组和体细胞超突变过程中的人类B细胞使用概率推理方法对人类B细胞受体重链的高通量DNA序列库。我们的分析捕获的统计特性的幼稚的剧目，首先通过VDJ重组后，然后选择功能后，其初始生成。我们还推断体细胞超突变机制的统计特性（不包括随后的选择效应）。我们的主要结果如下：由于较长的连接插入，B细胞库实质上比T细胞库更多样化;通过初始选择的序列通过具有在VDJ重组事件中产生的更高概率来区分;体细胞超突变具有非-沿着V基因的均匀分布，这可以通过超突变位点周围序列背景的独立位点模型很好地解释。
英文摘要：
We quantify the VDJ recombination and somatic hypermutation processes in human B-cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the statistical properties of the naive repertoire, first after its initial generation via VDJ recombination and then after selection for functionality. We also infer statistical properties of the somatic hypermutation machinery (exclusive of subsequent effects of selection). Our main results are the following: the B-cell repertoire is substantially more diverse than T-cell repertoires, due to longer junctional insertions; sequences that pass initial selection are distinguished by having a higher probability of being generated in a VDJ recombination event; somatic hypermutations have a non-uniform distribution along the V gene that is well explained by an independent site model for the sequence context around the hypermutation site.
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