{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:52:25Z","timestamp":1778633545968,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"24","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1105,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Dynamic simulation of genome-scale molecular interaction networks will enable the mechanistic prediction of genotype\u2013phenotype relationships. Despite advances in quantitative biology, full parameterization of whole-cell models is not yet possible. Simulation methods capable of using available qualitative data are required to develop dynamic whole-cell models through an iterative process of modelling and experimental validation.<\/jats:p>\n               <jats:p>Results: We formulate quasi-steady state Petri nets (QSSPN), a novel method integrating Petri nets and constraint-based analysis to predict the feasibility of qualitative dynamic behaviours in qualitative models of gene regulation, signalling and whole-cell metabolism. We present the first dynamic simulations including regulatory mechanisms and a genome-scale metabolic network in human cell, using bile acid homeostasis in human hepatocytes as a case study. QSSPN simulations reproduce experimentally determined qualitative dynamic behaviours and permit mechanistic analysis of genotype\u2013phenotype relationships.<\/jats:p>\n               <jats:p>Availability and implementation: The model and simulation software implemented in C++ are available in supplementary material and at http:\/\/sysbio3.fhms.surrey.ac.uk\/qsspn\/.<\/jats:p>\n               <jats:p>Contact: \u00a0a.kierzek@surrey.ac.uk<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btt552","type":"journal-article","created":{"date-parts":[[2013,9,25]],"date-time":"2013-09-25T03:45:09Z","timestamp":1380080709000},"page":"3181-3190","source":"Crossref","is-referenced-by-count":30,"title":["QSSPN: dynamic simulation of molecular interaction networks describing gene regulation, signalling and whole-cell metabolism in human cells"],"prefix":"10.1093","volume":"29","author":[{"given":"Ciar\u00e1n P.","family":"Fisher","sequence":"first","affiliation":[{"name":"Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, Surrey GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Plant","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, Surrey GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Bernadette","family":"Moore","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, Surrey GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej M.","family":"Kierzek","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, Surrey GU2 7XH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,9,23]]},"reference":[{"key":"2023012810481973100_btt552-B1","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1126\/science.1099390","article-title":"Bacterial persistence as a phenotypic switch","volume":"305","author":"Balaban","year":"2004","journal-title":"Science"},{"key":"2023012810481973100_btt552-B2","doi-asserted-by":"crossref","first-page":"e1000812","DOI":"10.1371\/journal.pcbi.1000812","article-title":"The carbon assimilation network in Escherichia coli is densely connected and largely sign-determined by directions of metabolic fluxes","volume":"6","author":"Baldazzi","year":"2010","journal-title":"PLoS Comput. 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