Esmaili-Taheri Ali, Ganjtabesh Mohammad
Department of Computer Science, School of Mathematics, Statistics, and Computer Science, College of Science, University of Tehran, Tehran, Iran.
Laboratoire d'Informatique (LIX), Ecole Polytechnique, Palaiseau CEDEX, 91128, France.
BMC Bioinformatics. 2015 Jan 28;16:20. doi: 10.1186/s12859-014-0444-5.
The function of an RNA in cellular processes is directly related to its structure. The free energy of RNA structure in another important key to its function as only some structures with a specific level of free energy can take part in cellular reactions. Therefore, to perform a specific function, a particular RNA structure with specific level of free energy is required. For a given RNA structure, the goal of the RNA design problem is to design an RNA sequence that folds into the given structure. To mimic the biological features of RNA sequences and structures, some sequence and energy constraints should be considered in designing RNA. Although the level of free energy is important, it is not considered in the available approaches for RNA design problem.
In this paper, we present a new version of our evolutionary algorithm for RNA design problem, entitled ERD, and extend it to handle some sequence and energy constraints. In the sequence constraints, one can restrict sequence positions to a fixed nucleotide or to a subset of nucleotides. As for the energy constraint, one can specify an interval for the free energy ranges of the designed sequences. We compare our algorithm with INFO-RNA, MODENA, NUPACK, and RNAiFold approaches for some artificial and natural RNA secondary structures and constraints.
The results indicate that our algorithm outperforms the other mentioned approaches in terms of accuracy, speedup, divergency, nucleotides distribution, and similarity to the natural RNA sequences. Particularly, the designed RNA sequences in our method are much more reliable and similar to the natural counterparts. The generated sequences are more diverse and they have closer nucleotides distribution to the natural one. The ERD tool and web server are freely available at http://mostafa.ut.ac.ir/corna/erd-cons/ .
RNA在细胞过程中的功能与其结构直接相关。RNA结构的自由能是其功能的另一个关键因素，因为只有某些具有特定自由能水平的结构才能参与细胞反应。因此，要执行特定功能，需要具有特定自由能水平的特定RNA结构。对于给定的RNA结构，RNA设计问题的目标是设计一个能折叠成给定结构的RNA序列。为了模拟RNA序列和结构的生物学特征，在设计RNA时应考虑一些序列和能量约束。虽然自由能水平很重要，但在现有的RNA设计问题方法中并未考虑。
在本文中，我们提出了一种用于RNA设计问题的进化算法新版本，名为ERD，并对其进行扩展以处理一些序列和能量约束。在序列约束方面，可以将序列位置限制为固定的核苷酸或核苷酸子集。至于能量约束，可以为设计序列的自由能范围指定一个区间。我们将我们的算法与INFO-RNA、MODENA、NUPACK和RNAiFold方法针对一些人工和天然RNA二级结构及约束进行了比较。
结果表明，我们的算法在准确性、加速比、发散性、核苷酸分布以及与天然RNA序列的相似性方面优于其他上述方法。特别是，我们方法中设计的RNA序列更可靠且与天然对应序列更相似。生成的序列更多样化，并且它们的核苷酸分布与天然序列更接近。ERD工具和网络服务器可在http://mostafa.ut.ac.ir/corna/erd-cons/ 免费获取。
