DIVIDE-CONQUER & AGGREGATE BASED APPROACH FOR EFFICIENT CHARACTERIZATION OF ALU

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 在大规模的DNA碱基序列上表征Alu元件的插入位点偏好性是灵长类特异信息学中的一个重要问题。这个问题具有挑战性和有趣的关键特征包括：1）在没有任何先验知识的情况下，我们能否发现可能存在的一般模式，并获得生物学见解？2)如何在4200或10120的搜索空间中获得紧凑而重要的判别模式？本研究提出一个整合分治与聚合为基础的演算法，成功地完成上述任务。与现有的最先进的生物学研究相比，我们对8400多个前Alu插入序列的研究结果表明，进一步细化分析的特征模式参与的Alu插入的机制。在生物学中最重要的是，我们获得了Alu插入周围的200 nt预测谱，其不仅包含广泛接受的信号共识，而且还表明了更长的模式（T）7AA [AG] AATAA。生物学意义在于，该模式提供了对有利的序列变异的更多了解，所述有利的序列变异允许通过参与启动插入过程的L1 ORF 2内切核酸酶进行优选的结合和切割。将相应地进行全基因组搜索，以确定所发现模式的分布。将获得的模式的全基因组位置与人类基因组上的基因分布进行比较，以确定哪些基因可能特别容易受到Alu插入突变的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Characterizing the insertion site preference of Alu elements on a large scale DNA bases is an important problem in primate-specific informatics. Key characteristics of this problem that are challenging and interesting include: 1) Without any prior knowledge, can we discover the general patterns that could exist and also make biological insights? 2) How to obtain the compact yet essential discriminative patterns given a search space up of 4200 or 10120? This research proposes an integrated divide-conquer and aggregate based algorithm for successfully fulfilling the above task. Compared to the existing state-of-the-art biological study, our results on over 8400 pre-Alu insertion sequences demonstrate a further refined analysis of the characteristic patterns involved in the mechanism of Alu insertion. Most importantly in biology, we acquire a 200nt predictive profile around the Alu insertion which not only contains the widely accepted signal consensus, but also suggests a longer pattern (T)7AA[AG]AATAA. The biological significance is that this pattern provides more insight into the favored sequence variations allowed for preferred binding and cleavage by the L1 ORF2 endonuclease that is involved in initiating the insertion process. Whole-genome search for the distribution of the discovered pattern will be conducted accordingly. The obtained genome-wide locations of the pattern will be compared to gene distributions on the human genome to identify which genes might be especially susceptible to the Alu insertion mutations.