{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:58:18Z","timestamp":1773665898232,"version":"3.50.1"},"reference-count":27,"publisher":"World Scientific Pub Co Pte Ltd","issue":"02","funder":[{"name":"Federal Agency for Scientific Organisations of the Russian Federation","award":["01201351572"],"award-info":[{"award-number":["01201351572"]}]},{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["15-04-07800"],"award-info":[{"award-number":["15-04-07800"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["15-04-06480"],"award-info":[{"award-number":["15-04-06480"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["16.8549.2017\/8.9"],"award-info":[{"award-number":["16.8549.2017\/8.9"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Bioinform. Comput. Biol."],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Commonly among the model parameters characterizing complex biological systems are those that do not significantly influence the quality of the fit to experimental data, so-called \u201csloppy\u201d parameters. The sloppiness can be mathematically expressed through saturating response functions (Hill\u2019s, sigmoid) thereby embodying biological mechanisms responsible for the system robustness to external perturbations. However, if a sloppy model is used for the prediction of the system behavior at the altered input (e.g. knock out mutations, natural expression variability), it may demonstrate the poor predictive power due to the ambiguity in the parameter estimates. We introduce a method of the predictive power evaluation under the parameter estimation uncertainty, Relative Sensitivity Analysis. The prediction problem is addressed in the context of gene circuit models describing the dynamics of segmentation gene expression in Drosophila embryo. Gene regulation in these models is introduced by a saturating sigmoid function of the concentrations of the regulatory gene products. We show how our approach can be applied to characterize the essential difference between the sensitivity properties of robust and non-robust solutions and select among the existing solutions those providing the correct system behavior at any reasonable input. In general, the method allows to uncover the sources of incorrect predictions and proposes the way to overcome the estimation uncertainties.<\/jats:p>","DOI":"10.1142\/s0219720018400085","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T10:33:44Z","timestamp":1516876424000},"page":"1840008","source":"Crossref","is-referenced-by-count":7,"title":["Relative sensitivity analysis of the predictive properties of sloppy models"],"prefix":"10.1142","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-1012","authenticated-orcid":false,"given":"Ekaterina","family":"Myasnikova","sequence":"first","affiliation":[{"name":"Center for Advanced Studies, St. Petersburg State Polytechnical University 29, Polytekhnicheskaya, St. Petersburg 195251, Russia"}]},{"given":"Alexander","family":"Spirov","sequence":"additional","affiliation":[{"name":"Computer Science and CEWIT, SUNY Stony Brook 1500 Stony Brook Road, Stony Brook, NY 11794, USA"},{"name":"Lab Modeling of Evolution I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry Russian Academy of Sciences, Pr. Torez 44, St. Petersburg 194223, Russia"}]}],"member":"219","published-online":{"date-parts":[[2018,5,8]]},"reference":[{"key":"S0219720018400085BIB001","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2008.06844.x"},{"key":"S0219720018400085BIB002","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-2-83"},{"key":"S0219720018400085BIB003","doi-asserted-by":"publisher","DOI":"10.1002\/9780470316757"},{"key":"S0219720018400085BIB004","series-title":"CMS Books in Mathematics","volume-title":"Generalized Inverses, Theory and Applications","author":"Ben-Israel A","year":"2003","edition":"2"},{"key":"S0219720018400085BIB005","doi-asserted-by":"publisher","DOI":"10.1029\/2000WR900350"},{"key":"S0219720018400085BIB006","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-4-142"},{"key":"S0219720018400085BIB007","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/1752-0509-5-118","volume":"5","author":"Gursky V","year":"2011","journal-title":"BMC Syst Biol"},{"key":"S0219720018400085BIB008","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0030189"},{"key":"S0219720018400085BIB009","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm382"},{"key":"S0219720018400085BIB011","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.027334"},{"key":"S0219720018400085BIB012","doi-asserted-by":"publisher","DOI":"10.1038\/nature02678"},{"key":"S0219720018400085BIB013","doi-asserted-by":"publisher","DOI":"10.1038\/ng1886"},{"key":"S0219720018400085BIB014","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002635"},{"key":"S0219720018400085BIB015","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000303"},{"key":"S0219720018400085BIB016","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000049"},{"key":"S0219720018400085BIB017","doi-asserted-by":"publisher","DOI":"10.1142\/S0219720014410029"},{"key":"S0219720018400085BIB018","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/17.1.3"},{"issue":"6","key":"S0219720018400085BIB019","first-page":"1054","volume":"62","author":"Myasnikova E","year":"2017","journal-title":"Biofizika"},{"key":"S0219720018400085BIB020","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp358"},{"key":"S0219720018400085BIB021","series-title":"Wiley Series in Probability and Statistics","volume-title":"Sensitivity Analysis","author":"Saltelli A","year":"2000"},{"key":"S0219720018400085BIB022","doi-asserted-by":"publisher","DOI":"10.1080\/00401706.1999.10485594"},{"key":"S0219720018400085BIB023","doi-asserted-by":"publisher","DOI":"10.1002\/9781119079453.ch10"},{"key":"S0219720018400085BIB024","doi-asserted-by":"publisher","DOI":"10.1142\/S0219720016410055"},{"key":"S0219720018400085BIB025","doi-asserted-by":"publisher","DOI":"10.1063\/1.4923066"},{"key":"S0219720018400085BIB026","first-page":"1130","volume":"8","author":"Vanlier J","year":"2011","journal-title":"Bioinformatics"},{"key":"S0219720018400085BIB027","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1242\/dev.129.7.1669","volume":"129","author":"Zhao C","year":"2002","journal-title":"Development"},{"key":"S0219720018400085BIB028","doi-asserted-by":"publisher","DOI":"10.1049\/iet-syb.2011.0015"}],"container-title":["Journal of Bioinformatics and Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.worldscientific.com\/doi\/pdf\/10.1142\/S0219720018400085","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T05:09:26Z","timestamp":1660367366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.worldscientific.com\/doi\/abs\/10.1142\/S0219720018400085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":27,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2018,5,8]]},"published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1142\/S0219720018400085"],"URL":"https:\/\/doi.org\/10.1142\/s0219720018400085","relation":{},"ISSN":["0219-7200","1757-6334"],"issn-type":[{"value":"0219-7200","type":"print"},{"value":"1757-6334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4]]}}}