{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:44:34Z","timestamp":1767339874770,"version":"3.32.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: Large biochemical networks pose a unique challenge from the point of view of evaluating conservation laws. The computational problem in most cases exceeds the capability of available software tools, often resulting in inaccurate computation of the number and form of conserved cycles. Such errors have profound effects on subsequent calculations, particularly in the evaluation of the Jacobian which is a critical quantity in many other calculations. The goal of this paper is to outline a new algorithm that is computationally efficient and robust at extracting the correct conservation laws for very large biochemical networks.<\/jats:p><jats:p>Results: We show that our algorithm can perform the conservation analysis of large biochemical networks, and can evaluate the correct conserved cycles when compared with other similar software tools. Biochemical simulators such as Jarnac and COPASI are successful at extracting only a subset of the conservation laws that our algorithm can. This is illustrated with examples for some large networks which show the advantages of our method.<\/jats:p><jats:p>Availability: The software is available as part of the latest release of Systems Biology Workbench (SBW version 2.5.0) and can be downloaded from . The software is licensed under the BSD open source license and is freely available at sourceforge.<\/jats:p><jats:p>Contact: \u00a0rrao@kgi.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/bti800","type":"journal-article","created":{"date-parts":[[2005,11,30]],"date-time":"2005-11-30T03:18:43Z","timestamp":1133320723000},"page":"346-353","source":"Crossref","is-referenced-by-count":61,"title":["Conservation analysis of large biochemical networks"],"prefix":"10.1093","volume":"22","author":[{"given":"Ravishankar Rao","family":"Vallabhajosyula","sequence":"first","affiliation":[{"name":"Keck Graduate Institute \u00a0 535 Watson Drive, Claremont, CA 91711, USA"}]},{"given":"Vijay","family":"Chickarmane","sequence":"additional","affiliation":[{"name":"Keck Graduate Institute \u00a0 535 Watson Drive, Claremont, CA 91711, USA"}]},{"given":"Herbert M.","family":"Sauro","sequence":"additional","affiliation":[{"name":"Keck Graduate Institute \u00a0 535 Watson Drive, Claremont, CA 91711, USA"}]}],"member":"286","published-online":{"date-parts":[[2005,11,29]]},"reference":[{"volume-title":"LAPACK User's Guide","year":"1995","author":"Anderson","key":"2023012408325051100_b1"},{"key":"2023012408325051100_b2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF00282276","article-title":"Prolegomena to the rational analysis of systems of chemical reactions","volume":"19","author":"Aris","year":"1965","journal-title":"Arch. Rational Mech. Anal."},{"key":"2023012408325051100_b3","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1093\/bioinformatics\/bti603","article-title":"Bifurcation discovery tool","volume":"21","author":"Chickarmane","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012408325051100_b4","doi-asserted-by":"crossref","DOI":"10.1002\/9780470142622.ch1","article-title":"Stability of complex reaction networks","volume-title":"Advances in Chemical Physics","author":"Clarke","year":"1980"},{"key":"2023012408325051100_b5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/jtbi.2002.2547","article-title":"The role of stoichiometric analysis in studies of metabolism: an example","volume":"216","author":"Cornish-Bowden","year":"2002","journal-title":"J. Theor. Biol."},{"key":"2023012408325051100_b6","article-title":"Stability of Householder QR factorization for weighted least squares problems","volume-title":"Numerical Analysis","author":"Cox","year":"1997"},{"key":"2023012408325051100_b7","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1142\/S0218127491000397","article-title":"Numerical analysis and control of bifurcation problems. Part I","volume":"1","author":"Doedel","year":"1991","journal-title":"Int. J. Bifurcat. Chaos"},{"key":"2023012408325051100_b8","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1101\/gr.2250904","article-title":"Reconstruction and validation of Saccharomyces cerevisiae iND750, a fully compartmentalized genome-scale metabolic model","volume":"14","author":"Duarte","year":"2004","journal-title":"Genome Res."},{"key":"2023012408325051100_b9","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1016\/0009-2509(89)85124-3","article-title":"Necessary and sufficient conditions for detailed balancing in mass action systems of arbitary complexity","volume":"44","author":"Feinberg","year":"1989","journal-title":"Chem. Eng. Sci."},{"key":"2023012408325051100_b10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S1478-5382(03)02370-9","article-title":"CellDesigner: a process diagram editor for gene-regulatory and biochemical networks","volume":"1","author":"Funahashi","year":"2003","journal-title":"BioSilico"},{"key":"2023012408325051100_b11","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/BF01436075","article-title":"Numerical methods for solving linear least-squares problems","volume":"7","author":"Golub","year":"1965","journal-title":"Numer. Math."},{"key":"2023012408325051100_b12","volume-title":"Matrix Computations","author":"Golub","year":"1996","edition":"3rd edn"},{"key":"2023012408325051100_b13","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1145\/130844.130851","article-title":"Householder reduction of linear equations","volume":"24","author":"Hansen","year":"1992","journal-title":"ACM Computing Surveys"},{"key":"2023012408325051100_b14","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4613-1161-4","volume-title":"The Regulation of Cellular Systems","author":"Heinrich","year":"1996"},{"key":"2023012408325051100_b15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0024-3795(99)00230-X","article-title":"QR factorization with complete pivoting and accurate computation of the SVD","volume":"209","author":"Higham","year":"2000","journal-title":"Linear Algebra Appl."},{"key":"2023012408325051100_b16","first-page":"5","article-title":"Steady-state modelling of metabolic pathways: a guide for the prospective simulator","volume":"2","author":"Hofmeyr","year":"1986","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408325051100_b17","first-page":"291","article-title":"Metabolic control analysis in a nutshell","author":"Hofmeyr","year":"2000"},{"key":"2023012408325051100_b18","first-page":"293","article-title":"A numerical treatment of metabolic control methods","volume-title":"Biothermokinetics","author":"Holstein","year":"1994"},{"key":"2023012408325051100_b19","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF00251225","article-title":"General mass action kinetics","author":"Horn","year":"1972","journal-title":"Arch. Rational Mech. Anal."},{"key":"2023012408325051100_b20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1145\/320941.320947","article-title":"Unitary triangularization of a nonsymmetric matrix","volume":"5","author":"Householder","year":"1958","journal-title":"J. ACM"},{"key":"2023012408325051100_b21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/BF01386370","article-title":"On certain methods for exapanding the characteristic polynomial","volume":"1","author":"Householder","year":"1959","journal-title":"Numerische Math."},{"key":"2023012408325051100_b22","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/bioinformatics\/btg015","article-title":"The Systems Biology Markup Language (SBML): a medium for representation and exchange of biochemical network models","volume":"19","author":"Hucka","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012408325051100_b23","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0301-4622(94)00104-R","article-title":"Control in channelled pathways. A matrix method calculating the enzyme control coefficients","volume":"53","author":"Kholodenko","year":"1995","journal-title":"Biophys. Chem."},{"article-title":"Stoichiometric analysis of metabolic networks","year":"2003","author":"Klamt","key":"2023012408325051100_b24"},{"key":"2023012408325051100_b25","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1126\/science.7089556","article-title":"Amplification and Adaptation in Regulatory and Sensory Systems","volume":"217","author":"Koshland","year":"1982","journal-title":"Science"},{"key":"2023012408325051100_b26","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0010-2180(92)90034-M","article-title":"Simplifying chemical kinetics: intrinsic low-dimensional manifolds in composition space","volume":"88","author":"Maas","year":"1992","journal-title":"Combustion Flame"},{"key":"2023012408325051100_b27","first-page":"563","article-title":"GEPASI: a software package for modelling the dynamics, steady states and control of biochemical and other systems","volume":"9","author":"Mendes","year":"1993","journal-title":"Comp. Appl. Biosci."},{"key":"2023012408325051100_b28","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1088\/1364-7830\/6\/4\/308","article-title":"A general algorithm for improving ILDMs","volume":"6","author":"Nafe","year":"2002","journal-title":"Combustion Theor. Modeling"},{"key":"2023012408325051100_b29","article-title":"Simulation and database software for computational systems biology: PySCeS and JWS Online","volume-title":"PhD Thesis","author":"Olivier","year":"2005"},{"key":"2023012408325051100_b30","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1093\/bioinformatics\/bti046","article-title":"Modelling cellular systems with PySCeS","volume":"21","author":"Olivier","year":"2005","journal-title":"Bioinformatics"},{"key":"2023012408325051100_b31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0022-5193(74)90139-8","article-title":"The hierarchical structure of metabolic networks and the construction of efficient metabolic simulators","volume":"46","author":"Park","year":"1974","journal-title":"J. Theor. Biol."},{"key":"2023012408325051100_b32","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0022-5193(88)80073-0","article-title":"Metabolic control theory: a structural approach","volume":"135","author":"Reder","year":"1988","journal-title":"J. Theor. Biol."},{"key":"2023012408325051100_b33","doi-asserted-by":"crossref","first-page":"R54.1","DOI":"10.1186\/gb-2003-4-9-r54","article-title":"An expanded genome-scale model of Escherichia coli K-12 (iJR904 GSM\/GPR)","volume":"4","author":"Reed","year":"2003","journal-title":"Genome Biol."},{"article-title":"Energy metabolism of the cell","year":"1981","author":"Reich","key":"2023012408325051100_b34"},{"key":"2023012408325051100_b35","first-page":"441","article-title":"SCAMP: a general-purpose simulator and metabolic control analysis program","volume":"9","author":"Sauro","year":"1993","journal-title":"Comput. Appl. Biosci."},{"key":"2023012408325051100_b36","first-page":"221","article-title":"Jarnac: a system for interactive metabolic analysis","volume-title":"Animating the Cellular Map. Intl. BioThermoKinetics Meeting","author":"Sauro","year":"2000"},{"article-title":"JDesigner: a simple biochemical network designer","year":"2001","author":"Sauro","key":"2023012408325051100_b37"},{"key":"2023012408325051100_b38","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1089\/153623103322637670","article-title":"Next generation simulation tools: the Systems Biology Workbench and BioSPICE integration","volume":"7","author":"Sauro","year":"2003","journal-title":"OMICS Winter"},{"key":"2023012408325051100_b39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bpc.2003.08.009","article-title":"Conservation analysis in biochemical networks: computational issues for software writers","volume":"109","author":"Sauro","year":"2004","journal-title":"Biophys. Chem."},{"key":"2023012408325051100_b40","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1128\/JB.184.16.4582-4593.2002","article-title":"Genome-scale metabolic model of Helicobacter pylori 26695","volume":"184","author":"Schilling","year":"2002","journal-title":"J. Bacteriol."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/3\/346\/48838327\/bioinformatics_22_3_346.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/22\/3\/346\/48838327\/bioinformatics_22_3_346.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:28:48Z","timestamp":1736123328000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/22\/3\/346\/220465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,29]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2006,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bti800","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"type":"electronic","value":"1367-4811"},{"type":"print","value":"1367-4803"}],"subject":[],"published-other":{"date-parts":[[2006,2,1]]},"published":{"date-parts":[[2005,11,29]]}}}