Selection of Target Sites for Mobile DNA Integration in the Human Genome

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.

逆转录病毒（retrovirus）、逆转录转座子（retrotransposon）、DNA转座子（DNA transposon）以及细小病毒（parvovirus）的DNA序列均可整合进入人类基因组。时至今日，此类序列的累积占人类基因组总序列的至少40%。这类整合元件同时也是人类基因治疗领域极具应用价值的基因递送载体。本研究针对HIV、MLV、ASLV、SFV、L1、SB及AAV的整合靶向性开展了全面的生物信息学分析。本研究借助超200种基因组注释数据，采用数学方法对人类基因组中每个碱基对的各类整合元件的整合概率进行了注释。本生物信息学资源揭示了大量基因组特征与整合靶向性之间的全新关联。本研究同时发现，所分析的基因组区间长度对所得结论具有显著影响——因此，若要解答“哪些基因组特征会影响整合过程”这一问题，需明确指定所关注的长度尺度。