title: RNA-TVcurve: a Web server for RNA secondary structure comparison based on a multi-scale similarity of its triple vector curve representation.
abstract: BACKGROUND
  RNAs have been found to carry diverse functionalities in nature. Inferring the similarity between two given RNAs is a fundamental step to understand and interpret their functional relationship. The majority of functional RNAs show conserved secondary structures, rather than sequence conservation. Those algorithms relying on sequence-based features usually have limitations in their prediction performance. Hence, integrating RNA structure features is very critical for RNA analysis. Existing algorithms mainly fall into two categories: alignment-based and alignment-free. The alignment-free algorithms of RNA comparison usually have lower time complexity than alignment-based algorithms.
  
  
  RESULTS
  An alignment-free RNA comparison algorithm was proposed, in which novel numerical representations RNA-TVcurve (triple vector curve representation) of RNA sequence and corresponding secondary structure features are provided. Then a multi-scale similarity score of two given RNAs was designed based on wavelet decomposition of their numerical representation. In support of RNA mutation and phylogenetic analysis, a web server (RNA-TVcurve) was designed based on this alignment-free RNA comparison algorithm. It provides three functional modules: 1) visualization of numerical representation of RNA secondary structure; 2) detection of single-point mutation based on secondary structure; and 3) comparison of pairwise and multiple RNA secondary structures. The inputs of the web server require RNA primary sequences, while corresponding secondary structures are optional. For the primary sequences alone, the web server can compute the secondary structures using free energy minimization algorithm in terms of RNAfold tool from Vienna RNA package.
  
  
  CONCLUSIONS
  RNA-TVcurve is the first integrated web server, based on an alignment-free method, to deliver a suite of RNA analysis functions, including visualization, mutation analysis and multiple RNAs structure comparison. The comparison results with two popular RNA comparison tools, RNApdist and RNAdistance, showcased that RNA-TVcurve can efficiently capture subtle relationships among RNAs for mutation detection and non-coding RNA classification. All the relevant results were shown in an intuitive graphical manner, and can be freely downloaded from this server. RNA-TVcurve, along with test examples and detailed documents, are available at: http://ml.jlu.edu.cn/tvcurve/ .
authors.affiliation: College of Computer Science and Technology, Jilin University, Changchun, 130012, China.|Key Laboratory of Symbolic Computation and Knowledge Engineering (Jilin University), Ministry of Education, Changchun, 130012, China.
authors.forename: Ying
authors.identifier: http://orcid.org/0000-0002-7804-149X
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Computer Science and Technology, Jilin University, Changchun, 130012, China.|Key Laboratory of Symbolic Computation and Knowledge Engineering (Jilin University), Ministry of Education, Changchun, 130012, China.
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Shi
authors.affiliation: College of Computer Science and Technology, Jilin University, Changchun, 130012, China.|Key Laboratory of Symbolic Computation and Knowledge Engineering (Jilin University), Ministry of Education, Changchun, 130012, China.|Zhuhai Laboratory of Key Laboratory of Symbol Computation and Knowledge Engineering of Ministry of Education, Zhuhai College of Jilin University, Zhuhai, 519041, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Mathematics and Statistics, South Dakota State University, Brookings, SD, 57007, USA.|Bioinformatics and Mathematical Biosciences Lab, Department of Agronomy, Horticulture and Plant Science, South Dakota State University, Brookings, SD, 57007, USA.|BioSNTR, Brookings, SD, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Xie
authors.affiliation: College of Computer Science and Technology, Jilin University, Changchun, 130012, China. zy26@jlu.edu.cn.|Key Laboratory of Symbolic Computation and Knowledge Engineering (Jilin University), Ministry of Education, Changchun, 130012, China. zy26@jlu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Mathematics and Statistics, South Dakota State University, Brookings, SD, 57007, USA. qin.ma@sdstate.edu.|Bioinformatics and Mathematical Biosciences Lab, Department of Agronomy, Horticulture and Plant Science, South Dakota State University, Brookings, SD, 57007, USA. qin.ma@sdstate.edu.|BioSNTR, Brookings, SD, USA. qin.ma@sdstate.edu.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000465:Algorithms; D001105:Archaea / Q000235:genetics; D001419:Bacteria / Q000235:genetics; D056890:Eukaryota / Q000235:genetics; D020407:Internet; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D017354:Point Mutation; D012313:RNA / Q000737:chemistry*; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D012984:Software
chemical_list: D012313:RNA
keywords: Multi-scale similarity; Numerical representations; Phylogenetic tree; RNA structure comparison; RNA-TVcurve