{"paper_id":"32d2a45d-9d2c-4d46-ac97-c5112786196a","body_text":"Computing Double-Pushout GraphTransformation Rules and Atom-to-Atom Mapsfrom KEGG RCLASS Data | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Computing Double-Pushout GraphTransformation Rules and Atom-to-Atom Mapsfrom KEGG RCLASS Data Nora Beier, Thomas Gatter, Jakob Lykke Andersen, Peter Florian Stadler This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6765982/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Jan, 2026 Read the published version in Algorithms for Molecular Biology → Version 1 posted 9 You are reading this latest preprint version Abstract Background: Atom-to-atom maps play an important role for many applications. However, they are often difficult to obtain. The KEGG reaction database does not provide atom-to-atom maps for its reactions and instead offers a description of local changes for pairs of reactant and product molecules in terms of so-called RCLASSes. Developed for classification purposes, RCLASS data are difficult to use for purposes such as the construction of atom-to atom maps or reactions rules. DPO graph transformation rules, on the other hand, work as a convenient and efficient representation in particular for these applications. The RCLASS data can be understood as collections of local graph patterns in the reactants and products of a reaction together with partial correspondences of atoms. The problem of converting RCLASS data into DPO rules therefore is a special case of the graph reconstruction problem, which consists in inferring a graph from a collection of subgraphs. Results: We developed laveau, a tool that computes explicit DPO rules from KEGG reactions and RCLASS data. The algorithm proceeds stepwisely, starting with a translation of individual RDM codes, specifically developed by the KEGG database, into equivalent RDM pattern graphs. Multiple RDM pattern graphs for the same RCLASS are then combined based on their embeddings into the reactant and product molecules, observing certain consistency conditions. In the final step, these combined pairwise patterns are merged into a pair of subgraphs of reactants and products, respectively. If RCLASSes connecting all pairs of reactant and product molecules are available, the complete reaction center(s) is/are contained in the union these subgraphs. The atom-to-atom map inherited from the RDM codes then defines a DPO transformation rule. Application of these rules to the reactants then yields complete atom-atom maps (AAMs). Starting from 3195 RCLASSes, laveau generates a total of 1232 DPO rules and 1594 AAMs. Conclusions: The laveau software makes it possible to extract local atom-to-atom maps from the RCLASSes of the KEGG database, covering a large set of enzyme-catalized reactions. The results are made available in the form of DPO rules for use in atom-level models of metabolic networks, filling a crucial gap in the available data. Atom-to-Atom Mapping RCLASS KEGG Double Push Out Rules Graph Reconstruction Graph Transformation Metabolic Reactions Reaction Rules Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 29 Jan, 2026 Read the published version in Algorithms for Molecular Biology → Version 1 posted Editorial decision: Revision requested 14 Aug, 2025 Reviews received at journal 13 Aug, 2025 Reviewers agreed at journal 23 Jul, 2025 Reviews received at journal 04 Jul, 2025 Reviewers agreed at journal 17 Jun, 2025 Reviewers invited by journal 11 Jun, 2025 Editor assigned by journal 04 Jun, 2025 Submission checks completed at journal 28 May, 2025 First submitted to journal 28 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-6765982\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":469857509,\"identity\":\"5113fb6c-0075-4a45-a4b5-cce2e6cfe387\",\"order_by\":0,\"name\":\"Nora 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Molecular Biology\",\"twitterHandle\":\"@BioMedCentral\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"BMC/SO AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Atom-to-Atom Mapping, RCLASS, KEGG, Double Push Out Rules, Graph Reconstruction, Graph Transformation, Metabolic Reactions, Reaction Rules\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-6765982/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-6765982/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u0026nbsp; \\u003c/strong\\u003eAtom-to-atom maps play an important role for many applications. However,\\u0026nbsp; they are often difficult to obtain. The KEGG reaction database does not\\u0026nbsp; provide atom-to-atom maps for its reactions and instead offers a\\u0026nbsp; description of local changes for pairs of reactant and product molecules\\u0026nbsp; in terms of so-called RCLASSes. Developed for classification purposes,\\u0026nbsp; RCLASS data are difficult to use for purposes such as the construction of\\u0026nbsp; atom-to atom maps or reactions rules. DPO graph transformation rules, on\\u0026nbsp; the other hand, work as a convenient and efficient representation in\\u0026nbsp; particular for these applications. The RCLASS data can be understood as\\u0026nbsp; collections of local graph patterns in the reactants and products of a\\u0026nbsp; reaction together with partial correspondences of atoms. The problem of\\u0026nbsp; converting RCLASS data into DPO rules therefore is a special case of the\\u0026nbsp; graph reconstruction problem, which consists in inferring a graph from a\\u0026nbsp; collection of subgraphs.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u0026nbsp; \\u003c/strong\\u003eWe developed laveau, a tool that computes explicit DPO rules\\u0026nbsp; from KEGG reactions and RCLASS data. The algorithm proceeds stepwisely, starting with a translation of individual RDM codes, specifically developed by the KEGG database, into equivalent RDM pattern graphs. Multiple RDM pattern graphs for the same RCLASS\\u0026nbsp; are then combined based on their embeddings into the reactant and product\\u0026nbsp; molecules, observing certain consistency conditions. In the final step,\\u0026nbsp; these combined pairwise patterns are merged into a pair of subgraphs of\\u0026nbsp; reactants and products, respectively. If RCLASSes connecting all pairs of\\u0026nbsp; reactant and product molecules are available, the complete reaction\\u0026nbsp; center(s) is/are contained in the union these subgraphs. The atom-to-atom\\u0026nbsp; map inherited from the RDM codes then defines a DPO transformation\\u0026nbsp; rule. Application of these rules to the reactants then yields complete\\u0026nbsp; atom-atom maps (AAMs). 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