Selection of target sites for mobile DNA integration in the human genome.
Selection of target sites for mobile DNA integration in the human genome.
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DOI：
10.1371/journal.pcbi.0020157
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发表时间：
2006-11-24
影响因子：
4.3
通讯作者：
Bushman FD
中科院分区：
文献类型：
--
作者：
Berry C;Hannenhalli S;Leipzig J;Bushman FD
来自逆转录病毒、逆转录转座子、DNA 转座子和细小病毒的 DNA 序列都可以整合到人类基因组中。此类序列的积累至少占我们今天基因组的 40%。这些整合元件也可作为人类基因治疗的基因传递载体。在这里，我们对 HIV、MLV、ASLV、SFV、L1、SB 和 AAV 的整合靶向进行了全面的生物信息学分析。我们使用了一种数学方法，利用 200 多种基因组注释类型，对人类基因组中的每个碱基对进行注释，以确定每种类型的元件发生整合事件的可能性。该生物信息资源记录了基因组特征和整合靶向之间的大量新关联。该研究还表明，分析的基因组间隔长度强烈影响得出的结论，从而回答了“哪些基因组特征影响整合？”的问题。需要仔细指定感兴趣的长度范围。许多类型的基因组寄生虫将其 DNA 序列插入人类基因组中。其中包括逆转录病毒，例如 HIV、转座子和腺相关病毒。这些整合元件对于插入新 DNA 后在人类基因组中引起的变化以及作为基因治疗中使用的基因传递载体非常重要。先前的研究已经生成了这些元件整合的基因组靶标序列。 Berry、Hannenhalli、Leipzig 和 Bushman 在此提出了一项全面的生物信息学分析，使他们能够注释人类基因组中的每个碱基对，以确定每种类型的元素引发整合事件的可能性。该资源应该有助于理解基因组进化和优化用于人类基因治疗的基因传递载体。
DNA sequences from retroviruses, retrotransposons, DNA transposons, and parvoviruses can all become integrated into the human genome. Accumulation of such sequences accounts for at least 40% of our genome today. These integrating elements are also of interest as gene-delivery vectors for human gene therapy. Here we present a comprehensive bioinformatic analysis of integration targeting by HIV, MLV, ASLV, SFV, L1, SB, and AAV. We used a mathematical method which allowed annotation of each base pair in the human genome for its likelihood of hosting an integration event by each type of element, taking advantage of more than 200 types of genomic annotation. This bioinformatic resource documents a wealth of new associations between genomic features and integration targeting. The study also revealed that the length of genomic intervals analyzed strongly affected the conclusions drawn—thus, answering the question “What genomic features affect integration?” requires carefully specifying the length scale of interest. Many types of genomic parasites insert their DNA sequences into the human genome. Among these are retroviruses such as HIV, transposons, and adeno-associated virus. These integrating elements are important for the changes they cause in the human genome upon insertion of new DNA, and as gene-delivery vehicles for use in gene therapy. Previous studies have generated sequences of genomic targets of integration by these elements. Here Berry, Hannenhalli, Leipzig, and Bushman present a comprehensive bioinformatic analysis that allows them to annotate each base pair in the human genome for its likelihood of hosting an integration event by each type of element. This resource should prove useful in understanding genomic evolution and optimizing gene delivery vectors for use in human gene therapy.
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逆转录病毒DNA整合：靶位点选择的病毒和细胞决定因素。
影响因子：
6.7
作者：
Lewinski, Mary K;Yamashita, Masahiro;Emerman, Michael;Ciuffi, Angela;Marshall, Heather;Crawford, Gregory;Collins, Francis;Shinn, Paul;Leipzig, Jeremy;Hannenhalli, Sridhar;Berry, Charles C;Ecker, Joseph R;Bushman, Frederic D
通讯作者：
Bushman, Frederic D
影响因子：
5.4
作者：
Barr, SD;Leipzig, J;Bushman, FD
通讯作者：
Bushman, FD
影响因子：
5.6
作者：
Liu, GY;Geurts, AM;Hackett, PB
通讯作者：
Hackett, PB
影响因子：
64.5
作者：
Gilbert, N;Lutz-Prigge, S;Moran, JV
通讯作者：
Moran, JV
影响因子：
11.4
作者：
Lampe, DJ;Churchill, MEA;Robertson, HM
通讯作者：
Robertson, HM