RCPred: RNA complex prediction as a constrained maximum weight clique problem

BackgroundRNAs can interact and form complexes, which have various biological roles. The secondary structure prediction of those complexes is a first step towards the identification of their 3D structure. We propose an original approach that takes advantage of the high number of RNA secondary structure and RNA-RNA interaction prediction tools. We formulate the problem of RNA complex prediction as the determination of the best combination (according to the free energy) of predicted RNA secondary structures and RNA-RNA interactions.ResultsWe model those predicted structures and interactions as a graph in order to have a combinatorial optimization problem that is a constrained maximum weight clique problem. We propose an heuristic based on Breakout Local Search to solve this problem and a tool, called RCPred, that returns several solutions, including motifs like internal and external pseudoknots. On a large number of complexes, RCPred gives competitive results compared to the methods of the state of the art.ConclusionsWe propose in this paper a method called RCPred for the prediction of several secondary structures of RNA complexes, including internal and external pseudoknots. As further works we will propose an improved computation of the global energy and the insertion of 3D motifs in the RNA complexes.

[1]  Rolf Backofen,et al.  PETcofold: predicting conserved interactions and structures of two multiple alignments of RNA sequences , 2010, Bioinform..

[2]  Nasrollah Moghaddam Charkari,et al.  RNA-RNA interaction prediction using genetic algorithm , 2014, Algorithms for Molecular Biology.

[3]  T. Steitz,et al.  Metals, Motifs, and Recognition in the Crystal Structure of a 5S rRNA Domain , 1997, Cell.

[4]  Peter F. Stadler,et al.  ViennaRNA Package 2.0 , 2011, Algorithms for Molecular Biology.

[5]  Marcello Pelillo,et al.  A Complementary Pivoting Approach to the Maximum Weight Clique Problem , 2002, SIAM J. Optim..

[6]  J. Vohradský,et al.  The suboptimal structures find the optimal RNAs: homology search for bacterial non-coding RNAs using suboptimal RNA structures , 2010, Nucleic acids research.

[7]  L. Jaeger,et al.  Multistrand RNA secondary structure prediction and nanostructure design including pseudoknots. , 2011, ACS nano.

[8]  Tatsuya Akutsu,et al.  An accessibility-incorporated method for accurate prediction of RNA–RNA interactions from sequence data , 2017, Bioinform..

[9]  Markus E. Nebel,et al.  Algebraic and Combinatorial Properties of Common RNA Pseudoknot Classes with Applications , 2012, J. Comput. Biol..

[10]  Patric R. J. Östergård,et al.  A New Algorithm for the Maximum-Weight Clique Problem , 1999, Electron. Notes Discret. Math..

[11]  Tatsuya Akutsu,et al.  Dynamic Programming Algorithms for RNA Structure Prediction with Binding Sites , 2010, Pacific Symposium on Biocomputing.

[12]  Michael Zuker,et al.  Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information , 1981, Nucleic Acids Res..

[13]  Jan Gorodkin,et al.  RIsearch: fast RNA–RNA interaction search using a simplified nearest-neighbor energy model , 2012, Bioinform..

[14]  Richard M. Karp,et al.  Reducibility Among Combinatorial Problems , 1972, 50 Years of Integer Programming.

[15]  Nikolay V. Dokholyan,et al.  Comparative Visualization of the RNA Suboptimal Conformational Ensemble In Vivo , 2017, Biophysical journal.

[16]  Jin-Kao Hao,et al.  Breakout local search for the quadratic assignment problem , 2013, Appl. Math. Comput..

[17]  Qinghua Wu,et al.  A review on algorithms for maximum clique problems , 2015, Eur. J. Oper. Res..

[18]  Robert Giegerich,et al.  The RNA shapes studio , 2014, Bioinform..

[19]  Fred W. Glover,et al.  Multi-neighborhood tabu search for the maximum weight clique problem , 2012, Annals of Operations Research.

[20]  Fariza Tahi,et al.  Bi-objective integer programming for RNA secondary structure prediction with pseudoknots , 2018, BMC Bioinformatics.

[21]  Anne Condon,et al.  RNA STRAND: The RNA Secondary Structure and Statistical Analysis Database , 2008, BMC Bioinformatics.

[22]  Rolf Backofen,et al.  Fast prediction of RNA-RNA interaction , 2009, Algorithms for Molecular Biology.

[23]  Randy Goebel,et al.  Approximating the maximum multiple RNA interaction problem , 2014, Theor. Comput. Sci..

[24]  David H. Mathews,et al.  NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure , 2009, Nucleic Acids Res..

[25]  Conrad Steenberg,et al.  NUPACK: Analysis and design of nucleic acid systems , 2011, J. Comput. Chem..

[26]  Stanislaw Gawiejnowicz.  Local search algorithms , 2008 .

[27]  Jan Gorodkin,et al.  The foldalign web server for pairwise structural RNA alignment and mutual motif search , 2005, Nucleic Acids Res..

[28]  Syed Ali Ahmed,et al.  Gibbs/MCMC Sampling for Multiple RNA Interaction with Sub-Optimal Solutions , 2019, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[29]  Bruce A. Shapiro,et al.  Multistrand Structure Prediction of Nucleic Acid Assemblies and Design of RNA Switches. , 2016, Nano letters.

[30]  T. Henkin,et al.  The T box mechanism: tRNA as a regulatory molecule , 2010, FEBS letters.

[31]  Rolf Backofen,et al.  IntaRNA: efficient prediction of bacterial sRNA targets incorporating target site accessibility and seed regions , 2008, Bioinform..

[32]  Wayne J. Pullan,et al.  Approximating the maximum vertex/edge weighted clique using local search , 2008, J. Heuristics.

[33]  Illya V. Hicks,et al.  Combinatorial Branch-and-Bound for the Maximum Weight Independent Set Problem , 2006 .

[34]  Süleyman Cenk Sahinalp,et al.  taveRNA: a web suite for RNA algorithms and applications , 2007, Nucleic Acids Res..

[35]  Tatsuya Akutsu,et al.  RactIP: fast and accurate prediction of RNA-RNA interaction using integer programming , 2010, Bioinform..

[36]  Kaizhong Zhang,et al.  RNA-RNA Interaction Prediction and Antisense RNA Target Search , 2006, J. Comput. Biol..

[37]  Alok Singh,et al.  A hybrid heuristic for the maximum clique problem , 2006, J. Heuristics.

[38]  Christian M. Reidys,et al.  RNA-RNA interaction prediction based on multiple sequence alignments , 2010, Bioinform..

[39]  A. Condon,et al.  Secondary structure prediction of interacting RNA molecules. , 2005, Journal of molecular biology.

[40]  Tatsuya Akutsu,et al.  IPknot: fast and accurate prediction of RNA secondary structures with pseudoknots using integer programming , 2011, Bioinform..

[41]  Xiaojun Xu,et al.  VfoldCPX Server: Predicting RNA-RNA Complex Structure and Stability , 2016, PloS one.

[42]  Mahassine Djelloul,et al.  Algorithmes de graphes pour la recherche de motifs récurrents dans les structures tertiaires d'ARN. (Graph algorithms for repetitive motifs search in RNA tertiary structures) , 2009 .

[43]  Jérôme Waldispühl,et al.  Towards 3D structure prediction of large RNA molecules: an integer programming framework to insert local 3D motifs in RNA secondary structure , 2012, Bioinform..