Milo Nimrod, Yogev Sivan, Ziv-Ukelson Michal
Department of Computer Science, Ben-Gurion University of the Negev, Be'er Sheva, Israel.
Department of Computer Science, Ben-Gurion University of the Negev, Be'er Sheva, Israel.
Methods. 2014 Oct 1;69(3):326-34. doi: 10.1016/j.ymeth.2014.06.002. Epub 2014 Jul 5.
The discovery and functional analysis of noncoding RNA (ncRNA) systems in different organisms motivates the development of tools for aiding ncRNA research. Several tools exist that search for occurrences of a given RNA structural profile in genomic sequences. Yet, there is a need for an "RNA BLAST" tool, i.e., a tool that takes a putative functional RNA sequence as input, and efficiently searches for similar sequences in genomic databases, taking into consideration potential secondary structure features of the input query sequence. This work aims at providing such a tool. Our tool, denoted StemSearch, is based on a structural representation of an RNA sequence by its potential stems. Potential stems in genomic sequences are identified in a preprocessing stage, and indexed. A user-provided query sequence is likewise processed, and stems from the target genomes that are similar to the query stems are retrieved from the index. Then, relevant genomic regions are identified and ranked according to their similarity to the query stem-set while enforcing conservation of cross-stem topology. Experiments using RFAM families show significantly improved recall for StemSearch over BLAST, with small loss of precision. We further demonstrate our system's capability to handle eukaryotic genomes by successfully searching for members of the 7SK family in chromosome 2 of the human genome. StemSearch is freely available on the web at: http://www.cs.bgu.ac.il/∼negevcb/StemSearch.
不同生物体中非编码RNA（ncRNA）系统的发现及功能分析推动了辅助ncRNA研究工具的开发。现已有多种工具可用于在基因组序列中搜索给定RNA结构特征的出现情况。然而，仍需要一种“RNA BLAST”工具，即一种以假定的功能性RNA序列作为输入，并在考虑输入查询序列潜在二级结构特征的情况下，在基因组数据库中高效搜索相似序列的工具。这项工作旨在提供这样一种工具。我们的工具名为StemSearch，它基于RNA序列通过其潜在茎干的结构表示。基因组序列中的潜在茎干在预处理阶段被识别并建立索引。用户提供的查询序列也同样经过处理，与查询茎干相似的目标基因组茎干从索引中检索出来。然后，根据与查询茎干集的相似性识别相关基因组区域并进行排序，同时确保跨茎拓扑结构的保守性。使用RFAM家族进行的实验表明，与BLAST相比，StemSearch的召回率显著提高，而精度仅有小幅损失。我们通过在人类基因组2号染色体中成功搜索7SK家族成员，进一步证明了我们系统处理真核基因组的能力。StemSearch可在以下网站免费获取：http://www.cs.bgu.ac.il/∼negevcb/StemSearch。
