Berry Charles, Hannenhalli Sridhar, Leipzig Jeremy, Bushman Frederic D
Department of Family and Preventive Medicine, School of Medicine, University of California San Diego, La Jolla, California, United States of America.
PLoS Comput Biol. 2006 Nov 24;2(11):e157. doi: 10.1371/journal.pcbi.0020157.
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.
来自逆转录病毒、逆转座子、DNA转座子和细小病毒的DNA序列都能整合到人类基因组中。如今,这类序列的累积至少占我们基因组的40%。这些整合元件作为人类基因治疗的基因传递载体也备受关注。在此,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。我们采用了一种数学方法,利用200多种基因组注释,对人类基因组中的每个碱基对承载每种元件整合事件的可能性进行注释。这种生物信息学资源记录了基因组特征与整合靶向之间大量新的关联。该研究还表明,所分析的基因组区间长度对得出的结论有很大影响——因此,回答“哪些基因组特征影响整合?”这个问题需要仔细指定感兴趣的长度尺度。