{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:32:04Z","timestamp":1772717524670,"version":"3.50.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T00:00:00Z","timestamp":1499817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Kinetics is key to understand many phenomena involving RNAs, such as co-transcriptional folding and riboswitches. Exact out-of-equilibrium studies induce extreme computational demands, leading state-of-the-art methods to rely on approximated kinetics landscapes, obtained using sampling strategies that strive to generate the key landmarks of the landscape topology. However, such methods are impeded by a large level of redundancy within sampled sets. Such a redundancy is uninformative, and obfuscates important intermediate states, leading to an incomplete vision of RNA dynamics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We introduce RNANR, a new set of algorithms for the exploration of RNA kinetics landscapes at the secondary structure level. RNANR considers locally optimal structures, a reduced set of RNA conformations, in order to focus its sampling on basins in the kinetic landscape. Along with an exhaustive enumeration, RNANR implements a novel non-redundant stochastic sampling, and offers a rich array of structural parameters. Our tests on both real and random RNAs reveal that RNANR allows to generate more unique structures in a given time than its competitors, and allows a deeper exploration of kinetics landscapes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>RNANR is freely available at https:\/\/project.inria.fr\/rnalands\/rnanr.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btx269","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T07:52:13Z","timestamp":1492674733000},"page":"i283-i292","source":"Crossref","is-referenced-by-count":15,"title":["Efficient approximations of RNA kinetics landscape using non-redundant sampling"],"prefix":"10.1093","volume":"33","author":[{"given":"Juraj","family":"Mich\u00e1lik","sequence":"first","affiliation":[{"name":"AMIB project, Inria Saclay, Palaiseau, France"},{"name":"LIX CNRS UMR 7161, Ecole Polytechnique, Palaiseau, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Touzet","sequence":"additional","affiliation":[{"name":"CNRS, CRIStAL (UMR 9189, University of Lille), Villeneuve d\u2019Ascq, France"},{"name":"Bonsai project, Inria Lille-Nord Europe, Villeneuve d\u2019Ascq, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yann","family":"Ponty","sequence":"additional","affiliation":[{"name":"AMIB project, Inria Saclay, Palaiseau, France"},{"name":"LIX CNRS UMR 7161, Ecole Polytechnique, Palaiseau, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,7,12]]},"reference":[{"key":"2023051506485361700_btx269-B1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0166-218X(00)00186-4","article-title":"Dynamic programming algorithms for RNA secondary structure prediction with pseudoknots","volume":"104","author":"Akutsu","year":"2000","journal-title":"Discrete Appl. Math"},{"key":"2023051506485361700_btx269-B2","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1186\/1471-2105-9-340","article-title":"RNA strand: the RNA secondary structure and statistical analysis database","volume":"9","author":"Andronescu","year":"2008","journal-title":"BMC Bioinf"},{"key":"2023051506485361700_btx269-B3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/bs.mie.2014.10.060","volume-title":"Computational Methods for Understanding Riboswitches, Volume 553 of Methods in Enzymology","author":"Badelt","year":"2015"},{"key":"2023051506485361700_btx269-B4","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/emboj\/16.3.599","article-title":"Viroid processing: switch from cleavage to ligation is driven by a change from a tetraloop to a loop e conformation","volume":"16","author":"Baumstark","year":"1997","journal-title":"EMBO J"},{"key":"2023051506485361700_btx269-B5","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1261\/rna.049965.115","article-title":"RNA world research-still evolving","volume":"21","author":"Cech","year":"2015","journal-title":"RNA (New York, N.Y.)"},{"key":"2023051506485361700_btx269-B6","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nmeth.1603","article-title":"Sequence-based identification of 3d structural modules in RNA with rmdetect","volume":"8","author":"Cruz","year":"2011","journal-title":"Nat. Methods"},{"key":"2023051506485361700_btx269-B7","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1142\/S0219720006001904","article-title":"RNAkinetics: a web server that models secondary structure kinetics of an elongating RNA","volume":"4","author":"Danilova","year":"2006","journal-title":"J. Bioinf. Comput. Biol"},{"key":"2023051506485361700_btx269-B8","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1016\/j.tcs.2010.05.010","article-title":"Controlled non-uniform random generation of decomposable structures","volume":"411","author":"Denise","year":"2010","journal-title":"Theoret. Comput. Sci"},{"key":"2023051506485361700_btx269-B9","doi-asserted-by":"crossref","first-page":"7280","DOI":"10.1093\/nar\/gkg938","article-title":"A statistical sampling algorithm for RNA secondary structure prediction","volume":"31","author":"Ding","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"2023051506485361700_btx269-B10","first-page":"243","author":"du Boisberranger","year":"2012"},{"key":"2023051506485361700_btx269-B11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0304-3975(94)90226-7","article-title":"Calculus for the random generation of labelled combinatorial structures","volume":"132","author":"Flajolet","year":"1994","journal-title":"Theoret. Comput. Sci"},{"key":"2023051506485361700_btx269-B12","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00706-008-0895-3","article-title":"Beyond energy minimization: approaches to the kinetic folding of RNA","volume":"139","author":"Flamm","year":"2008","journal-title":"Monatshefte F\u00fcr Chemie Chem. Mon"},{"key":"2023051506485361700_btx269-B13","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1017\/S1355838200992161","article-title":"RNA folding at elementary step resolution","volume":"6","author":"Flamm","year":"2000","journal-title":"RNA (New York, N.Y.)"},{"key":"2023051506485361700_btx269-B14","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1017\/S1355838201000863","article-title":"Design of multistable RNA molecules","volume":"7","author":"Flamm","year":"2001","journal-title":"RNA (New York, N.Y.)"},{"key":"2023051506485361700_btx269-B15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1524\/zpch.2002.216.2.155","article-title":"Barrier trees of degenerate landscapes","volume":"216","author":"Flamm","year":"2002","journal-title":"Zeitschrift F\u00fcr Physikalische Chemie"},{"key":"2023051506485361700_btx269-B16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ymeth.2009.06.005","article-title":"The jerky and knotty dynamics of RNA","volume":"49","author":"Isambert","year":"2009","journal-title":"Methods (San Diego, Calif.)"},{"key":"2023051506485361700_btx269-B17","first-page":"2009","article-title":"Basin hopping graph: a computational framework to characterize RNA folding landscapes","volume":"30","author":"Kucharik","year":"2014","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023051506485361700_btx269-B18","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1021\/acssynbio.5b00297","article-title":"Using RNA as molecular code for programming cellular function","volume":"5","author":"Kushwaha","year":"2016","journal-title":"ACS Synth. Biol"},{"key":"2023051506485361700_btx269-B19","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1098\/rsfs.2011.0040","article-title":"Nucleic acid-based nanoengineering: novel structures for biomedical applications","volume":"1","author":"Li","year":"2011","journal-title":"Interface Focus"},{"key":"2023051506485361700_btx269-B20","first-page":"2994","article-title":"Finding stable local optimal RNA secondary structures","volume":"27","author":"Li","year":"2011","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2023051506485361700_btx269-B21","first-page":"11","volume-title":"German Conference on Bioinformatics 2009, Volume 157 of Lecture Notes in Informatics","author":"Lorenz","year":"2009"},{"key":"2023051506485361700_btx269-B22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1748-7188-6-26","article-title":"ViennaRNA package 2.0","volume":"6","author":"Lorenz","year":"2011","journal-title":"Algorithms Mol. Biol. AMB"},{"key":"2023051506485361700_btx269-B23","doi-asserted-by":"crossref","first-page":"e16178","DOI":"10.1371\/journal.pone.0016178","article-title":"Computing the partition function for kinetically trapped RNA secondary structures","volume":"6","author":"Lorenz","year":"2011","journal-title":"PLoS One"},{"key":"2023051506485361700_btx269-B24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.tcs.2013.01.006","article-title":"Non-redundant random generation algorithms for weighted context-free grammars","volume":"502","author":"Lorenz","year":"2013","journal-title":"Theoret. Comput. Sci"},{"key":"2023051506485361700_btx269-B25","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s11047-010-9239-4","article-title":"Np-completeness of the energy barrier problem without pseudoknots and temporary arcs","volume":"10","author":"Ma\u0148uch","year":"2011","journal-title":"Nat. Comput"},{"key":"2023051506485361700_btx269-B26","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1261\/rna.7650904","article-title":"Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization","volume":"10","author":"Mathews","year":"2004","journal-title":"RNA (New York, N.Y.)"},{"key":"2023051506485361700_btx269-B27","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/bip.360290621","article-title":"The equilibrium partition function and base pair binding probabilities for RNA secondary structure","volume":"29","author":"McCaskill","year":"1990","journal-title":"Biopolymers"},{"key":"2023051506485361700_btx269-B28","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1261\/rna.049502.114","article-title":"RNA-puzzles round ii: assessment of RNA structure prediction programs applied to three large RNA structures","volume":"21","author":"Miao","year":"2015","journal-title":"RNA (New York, N.Y.)"},{"key":"2023051506485361700_btx269-B29","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1088\/0305-4470\/31\/14\/005","article-title":"Barrier heights between ground states in a model of RNA secondary structure","volume":"31","author":"Morgan","year":"1998","journal-title":"J. Phys. A Math. Gen"},{"key":"2023051506485361700_btx269-B30","doi-asserted-by":"crossref","first-page":"D130","DOI":"10.1093\/nar\/gku1063","article-title":"Rfam 12.0: updates to the RNA families database","volume":"43","author":"Nawrocki","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2023051506485361700_btx269-B31","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1073\/pnas.77.11.6309","article-title":"Fast algorithm for predicting the secondary structure of single-stranded RNA","volume":"77","author":"Nussinov","year":"1980","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"2023051506485361700_btx269-B32","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1089\/cmb.2010.0178","article-title":"RNA locally optimal secondary structures","volume":"19","author":"Saffarian","year":"2012","journal-title":"J. Comput. Biol. J. Comput. Mol. Cell Biol"},{"key":"2023051506485361700_btx269-B33","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1126\/science.289.5478.448","article-title":"One sequence, two ribozymes: implications for the emergence of new ribozyme folds","volume":"289","author":"Schultes","year":"2000","journal-title":"Science (New York, N.Y.)"},{"key":"2023051506485361700_btx269-B34","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00285-014-0760-4","article-title":"RNA folding pathways and kinetics using 2d energy landscapes","volume":"70","author":"Senter","year":"2015","journal-title":"J. Math. Biol"},{"key":"2023051506485361700_btx269-B35","first-page":"45","article-title":"Database for mRNA half-life of 19\u2009977 genes obtained by DNA microarray analysis of pluripotent and differentiating mouse embryonic stem cells","volume":"16","author":"Sharova","year":"2009","journal-title":"DNA Res. Int. J. Rapid Publ. Rep. Genes Genomes"},{"key":"2023051506485361700_btx269-B36","first-page":"321","volume-title":"Combinatorial Pattern Matching, Volume 7354 of Lecture Notes in Computer Science","author":"Sheikh","year":"2012"},{"key":"2023051506485361700_btx269-B37","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1038\/nprot.2015.103","article-title":"Selective 2\u2019-hydroxyl acylation analyzed by primer extension and mutational profiling (shape-map) for direct, versatile and accurate RNA structure analysis","volume":"10","author":"Smola","year":"2015","journal-title":"Nat. Protoc"},{"key":"2023051506485361700_btx269-B38","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1006\/jmbi.1999.3001","article-title":"How RNA folds","volume":"293","author":"Tinoco","year":"1999","journal-title":"J. Mol. Biol"},{"key":"2023051506485361700_btx269-B39","doi-asserted-by":"crossref","first-page":"D280","DOI":"10.1093\/nar\/gkp892","article-title":"Nndb: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure","volume":"38","author":"Turner","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"2023051506485361700_btx269-B40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev.bb.17.060188.001123","article-title":"RNA structure prediction","volume":"17","author":"Turner","year":"1988","journal-title":"Annu. Rev. Biophys. Biophys. Chem"},{"key":"2023051506485361700_btx269-B41","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1089\/cmb.2006.0012","article-title":"Computing the partition function and sampling for saturated secondary structures of RNA, with respect to the turner energy model","volume":"14","author":"Waldisp\u00fchl","year":"2007","journal-title":"J. Comput. Biol. J. Comput. Mol. Cell Biol"},{"key":"2023051506485361700_btx269-B42","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/nsmb.3316","article-title":"Cotranscriptional folding of a riboswitch at nucleotide resolution","volume":"23","author":"Watters","year":"2016","journal-title":"Nat. Struct. Mol. Biol"},{"key":"2023051506485361700_btx269-B43","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1371\/journal.pbio.0060096","article-title":"High-throughput shape analysis reveals structures in hiv-1 genomic RNA strongly conserved across distinct biological states","volume":"6","author":"Wilkinson","year":"2008","journal-title":"PLoS Biol"},{"key":"2023051506485361700_btx269-B44","doi-asserted-by":"crossref","DOI":"10.1088\/0305-4470\/37\/17\/005","article-title":"Efficient computation of RNA folding dynamics","volume":"37","author":"Wolfinger","year":"2004","journal-title":"J. Phys. A Math"},{"key":"2023051506485361700_btx269-B45","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1097-0282(199902)49:2<145::AID-BIP4>3.0.CO;2-G","article-title":"Complete suboptimal folding of RNA and the stability of secondary structures","volume":"49","author":"Wuchty","year":"1999","journal-title":"Biopol"},{"key":"2023051506485361700_btx269-B46","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/nar\/gkl1036","article-title":"Encoding folding paths of RNA switches","volume":"35","author":"Xayaphoummine","year":"2007","journal-title":"Nucleic Acids Res"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/14\/i283\/50314613\/bioinformatics_33_14_i283.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/33\/14\/i283\/50314613\/bioinformatics_33_14_i283.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T06:49:35Z","timestamp":1684133375000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/33\/14\/i283\/3953986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,12]]},"references-count":46,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2017,7,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btx269","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"value":"1367-4803","type":"print"},{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,7,15]]},"published":{"date-parts":[[2017,7,12]]}}}