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Model reduction can help tame such complexity by providing a lower-dimensional model in which each macro-variable can be directly related to the original variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We present CLUE, an algorithm for exact model reduction of systems of polynomial differential equations by constrained linear lumping. It computes the smallest dimensional reduction as a linear mapping of the state space such that the reduced model preserves the dynamics of user-specified linear combinations of the original variables. Even though CLUE works with non-linear differential equations, it is based on linear algebra tools, which makes it applicable to high-dimensional models. Using case studies from the literature, we show how CLUE can substantially lower model dimensionality and help extract biologically intelligible insights from the reduction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>An implementation of the algorithm and relevant resources to replicate the experiments herein reported are freely available for download at https:\/\/github.com\/pogudingleb\/CLUE.<\/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\/btab010","type":"journal-article","created":{"date-parts":[[2021,1,30]],"date-time":"2021-01-30T20:08:53Z","timestamp":1612037333000},"page":"1732-1738","source":"Crossref","is-referenced-by-count":15,"title":["CLUE: exact maximal reduction of kinetic models by constrained lumping of differential equations"],"prefix":"10.1093","volume":"37","author":[{"given":"Alexey","family":"Ovchinnikov","sequence":"first","affiliation":[{"name":"Department of Mathematics, CUNY Queens College , Queens, NY 11367, USA"},{"name":"Ph.D. Programs in Mathematics and Computer Science, CUNY Graduate Center , New York, NY 10016, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"P\u00e9rez Verona","sequence":"additional","affiliation":[{"name":"IMT School for Advanced Studies , Lucca 55100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5731-8242","authenticated-orcid":false,"given":"Gleb","family":"Pogudin","sequence":"additional","affiliation":[{"name":"LIX, CNRS, \u00c9cole Polytechnique, Institute Polytechnique de Paris , Palaiseau 91120, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6018-5989","authenticated-orcid":false,"given":"Mirco","family":"Tribastone","sequence":"additional","affiliation":[{"name":"IMT School for Advanced Studies , Lucca 55100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"2023051800333727100_btab010-B1","doi-asserted-by":"crossref","DOI":"10.1137\/1.9780898718713","volume-title":"Approximation of Large-Scale Dynamical Systems. 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