ScanFold: an approach for genome-wide discovery of local RNA structural elements-applications to Zika virus and HIV
ScanFold: an approach for genome-wide discovery of local RNA structural elements-applications to Zika virus and HIV
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DOI：
10.7717/peerj.6136
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发表时间：
2018-12-18
期刊：
影响因子：
2.7
通讯作者：
Moss, Walter N.
中科院分区：
文献类型：
--
作者：
Andrews, Ryan J.;Roche, Julien;Moss, Walter N.
除了编码RNA一级结构外，基因组还编码RNA二级和三级结构，这些结构在基因调控中发挥作用，对于RNA病毒来说，还起到基因组复制的作用。识别基因组中功能RNA结构的方法通常依赖于扫描分析窗口，其中多个部分重叠的窗口被用来预测RNA结构和折叠度量来推断可能形成功能结构的区域。为每个窗口生成单独的结构模型，其中步长会对返回的模型产生很大影响。这使得推断独特的局部结构具有挑战性，因为每个窗口中的相同核苷酸可以交替碱基配对。我们在这里提出了一种新的方法，其中来自分析窗口的所有碱基对都被考虑并通过有利的折叠来加权。这导致了整个基因组中独特的碱基配对，并产生了局部区域/结构，这些区域/结构可以根据它们形成异常热力学稳定折叠的倾向进行排序。我们将这种方法应用于寨卡病毒(ZIKV)和HIV-1基因组。ZIKV与包括小头症和格林-巴利综合征在内的多种神经系统疾病有关，其(+)正义RNA基因组编码两个先前描述的功能必需的结构RNA区域。人类免疫缺陷病毒(HIV)是艾滋病的病原体，其基因组中含有多种功能RNA基序，已被广泛研究。我们的方法能够成功地识别和模拟这两种病毒中已知的功能基序的结构，同时还能够找到更多可能形成功能结构的区域。所有数据都已存档在RNAStryromeDB(www.structurome.bb.iastate.edu)中，这是一个人类及其病原体的RNA折叠数据存储库。
In addition to encoding RNA primary structures, genomes also encode RNA secondary and tertiary structures that play roles in gene regulation and, in the case of RNA viruses, genome replication. Methods for the identification of functional RNA structures in genomes typically rely on scanning analysis windows, where multiple partially-overlapping windows are used to predict RNA structures and folding metrics to deduce regions likely to form functional structure. Separate structural models are produced for each window, where the step size can greatly affect the returned model. This makes deducing unique local structures challenging, as the same nucleotides in each window can be alternatively base paired. We are presenting here a new approach where all base pairs from analysis windows are considered and weighted by favorable folding. This results in unique base pairing throughout the genome and the generation of local regions/structures that can be ranked by their propensity to form unusually thermodynamically stable folds. We applied this approach to the Zika virus (ZIKV) and HIV-1 genomes. ZIKV is linked to a variety of neurological ailments including microcephaly and Guillain-Barre syndrome and its (+)-sense RNA genome encodes two, previously described, functionally essential structured RNA regions. HIV, the cause of AIDS, contains multiple functional RNA motifs in its genome, which have been extensively studied. Our approach is able to successfully identify and model the structures of known functional motifs in both viruses, while also finding additional regions likely to form functional structures. All data have been archived at the RNAStructuromeDB (www.structurome.bb.iastate.edu), a repository of RNA folding data for humans and their pathogens.