Michigan State University, East Lansing, MI 48824, USA.
IEEE/ACM Trans Comput Biol Bioinform. 2013 Mar-Apr;10(2):274-85. doi: 10.1109/TCBB.2012.137.
Noncoding RNA (ncRNA) identification is highly important to modern biology. The state-of-the-art method for ncRNA identification is based on comparative genomics, in which evolutionary conservations of sequences and secondary structures provide important evidence for ncRNA search. For ncRNAs with low sequence conservation but high structural similarity, conventional local alignment tools such as BLAST yield low sensitivity. Thus, there is a need for ncRNA search methods that can incorporate both sequence and structural similarities. We introduce chain-RNA, a pairwise structural alignment tool that can effectively locate cross-species conserved RNA elements with low sequence similarity. In chain-RNA, stem-loop structures are extracted from dot plots generated by an efficient local-folding algorithm. Then, we formulate stem alignment as an extended 2D chain problem and employ existing chain algorithms. Chain-RNA is tested on a data set containing annotated ncRNA homologs and is applied to novel ncRNA search in a transcriptomic data set. The experimental results show that chain-RNA has better tradeoff between sensitivity and false positive rate in ncRNA prediction than conventional sequence similarity search tools and is more time efficient than structural alignment tools. The source codes of chain-RNA can be downloaded at http://sourceforge.net/projects/chain-rna/ or at http://www.cse.msu.edu/~leijikai/chain-rna/.
非编码 RNA (ncRNA) 的鉴定对现代生物学非常重要。ncRNA 鉴定的最新方法基于比较基因组学，其中序列和二级结构的进化保守性为 ncRNA 搜索提供了重要证据。对于序列保守性低但结构相似性高的 ncRNAs，传统的局部比对工具（如 BLAST）的灵敏度较低。因此，需要开发能够结合序列和结构相似性的 ncRNA 搜索方法。我们引入了 chain-RNA，这是一种能够有效定位具有低序列相似性的跨物种保守 RNA 元件的成对结构比对工具。在 chain-RNA 中，茎环结构是从通过高效局部折叠算法生成的点图中提取的。然后，我们将茎对齐形式化地表示为扩展的 2D 链问题，并采用现有的链算法。我们在包含注释 ncRNA 同源物的数据集上对 chain-RNA 进行了测试，并将其应用于转录组数据集中的新 ncRNA 搜索。实验结果表明，与传统的序列相似性搜索工具相比，chain-RNA 在 ncRNA 预测中的灵敏度和假阳性率之间具有更好的权衡，并且比结构比对工具更节省时间。chain-RNA 的源代码可以在以下网址下载：http://sourceforge.net/projects/chain-rna/ 或 http://www.cse.msu.edu/~leijikai/chain-rna/。
