The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure.
The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure.
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DOI：
10.1186/s12859-018-2161-y
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发表时间：
2018-05-02
影响因子：
3
通讯作者：
MacCarthy T
中科院分区：
文献类型：
--
作者：
Shapiro M;Meier S;MacCarthy T
活化诱导脱氨酶(AID)和载脂蛋白B信使核糖核酸编辑酶，催化多肽样3(APOBEC3)是单链DNA(SsDNA)上C位突变为U位的脱氨酶。AID主要在生发中心B细胞表达，在那里它促进亲和力成熟和类开关重组。APOBEC3是一个抗病毒蛋白家族，作为内在免疫反应的一部分。在这两种情况下，都有特定的序列基序，也被称为“突变基序”，这些脱氨酶更喜欢与之结合和突变。我们提出了一个程序，胞苷脱氨酶低表达报告(CDUR)，旨在统计地确定给定的序列是否具有这些突变基序的低表达/高表达。CDUR显示出与其他对突变基序的研究一致，正如我们通过分析腺相关病毒2(AAV2)和人乳头状瘤病毒(HPV)的序列所显示的那样。使用各种改组机制来生成不同的空模型分布，我们可以定制CDUR以校正诸如GC含量、二核苷酸频率和密码子偏差等指标。
Activation induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) are deaminases that mutate C to U on single-stranded DNA (ssDNA). AID is expressed primarily in germinal center B-cells, where it facilitates affinity maturation and class-switch recombination. APOBEC3 are a family of anti-viral proteins that act as part of the intrinsic immune response. In both cases, there are particular sequence motifs, also known as “mutation motifs”, to which these deaminases prefer to bind and mutate. We present a program, the cytidine deaminase under-representation reporter (CDUR) designed to statistically determine whether a given sequence has an under/over-representation of these mutation motifs. CDUR shows consitency with other studies of mutation motifs, as we show by analyzing sequences from the adeno-associated virus 2 (AAV2) and human papillomavirus (HPV). Using various shuffling mechanisms to generate different null model distributions, we can tailor CDUR to correct for metrics such as GC-content, dinucleotide frequency, and codon bias.
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