{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T02:26:40Z","timestamp":1769826400532,"version":"3.49.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2019,3,28]],"date-time":"2019-03-28T00:00:00Z","timestamp":1553731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM076485"],"award-info":[{"award-number":["R01GM076485"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Predicting the secondary structure of RNA is a fundamental task in bioinformatics. Algorithms that predict secondary structure given only the primary sequence, and a model to evaluate the quality of a structure, are an integral part of this. These algorithms have been updated as our model of RNA thermodynamics changed and expanded. An exception to this has been the treatment of multi-loops. Although more advanced models of multi-loop free energy change have been suggested, a simple, linear model has been used since the 1980s. However, recently, new dynamic programing algorithms for secondary structure prediction that could incorporate these models were presented. Unfortunately, these models appear to have lower accuracy for secondary structure prediction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We apply linear regression and a new parameter optimization algorithm to find better parameters for the existing linear model and advanced non-linear multi-loop models. These include the Jacobson-Stockmayer and Aalberts &amp; Nandagopal models. We find that the current linear model parameters may be near optimal for the linear model, and that no advanced model performs better than the existing linear model parameters even after parameter optimization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>Source code and data is available at https:\/\/github.com\/maxhwardg\/advanced_multiloops.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz222","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T21:26:30Z","timestamp":1553721990000},"page":"4298-4306","source":"Crossref","is-referenced-by-count":9,"title":["Determining parameters for non-linear models of multi-loop free energy change"],"prefix":"10.1093","volume":"35","author":[{"given":"Max","family":"Ward","sequence":"first","affiliation":[{"name":"Computer Science & Software Engineering, The University of Western Australia , Crawley, WA, Australia"}]},{"given":"Hongying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Biophysics, University of Rochester , Rochester, NY, USA"},{"name":"Center for RNA Biology, University of Rochester , Rochester, NY, USA"}]},{"given":"Amitava","family":"Datta","sequence":"additional","affiliation":[{"name":"Computer Science & Software Engineering, The University of Western Australia , Crawley, WA, Australia"}]},{"given":"Michael","family":"Wise","sequence":"additional","affiliation":[{"name":"Computer Science & Software Engineering, The University of Western Australia , Crawley, WA, Australia"},{"name":"The Marshall Centre for Infectious Diseases Research and Training, The University of Western Australia , Crawley, WA, Australia"}]},{"given":"David H","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Biostatistics & Computational Biology, University of Rochester , Rochester, NY, USA"}]}],"member":"286","published-online":{"date-parts":[[2019,3,28]]},"reference":[{"key":"2023062712532024000_btz222-B1","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1261\/rna.1831710","article-title":"A two-length-scale polymer theory for RNA loop free energies and helix stacking","volume":"16","author":"Aalberts","year":"2010","journal-title":"RNA"},{"key":"2023062712532024000_btz222-B2","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4612-1694-0_15","volume-title":"Information Theory and an Extension of the Maximum Likelihood Principle","author":"Akaike","year":"1998"},{"key":"2023062712532024000_btz222-B3","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1126\/science.1155472","article-title":"The eukaryotic genome as an RNA machine","volume":"319","author":"Amaral","year":"2008","journal-title":"Science"},{"key":"2023062712532024000_btz222-B4","doi-asserted-by":"crossref","first-page":"i19","DOI":"10.1093\/bioinformatics\/btm223","article-title":"Efficient parameter estimation for RNA secondary structure prediction","volume":"23","author":"Andronescu","year":"2007","journal-title":"Bioinformatics"},{"key":"2023062712532024000_btz222-B5","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 Bioinformatics"},{"key":"2023062712532024000_btz222-B6","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1261\/rna.1950510","article-title":"Computational approaches for RNA energy parameter estimation","volume":"16","author":"Andronescu","year":"2010","journal-title":"RNA"},{"key":"2023062712532024000_btz222-B7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/978-1-62703-709-9_3","article-title":"The determination of RNA folding nearest neighbor parameters","volume":"1097","author":"Andronescu","year":"2014","journal-title":"Methods Mol. 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