Simplifications and approximations in molecular systems biology: lessons from a single-gene circuit

Simplifications and approximations in molecular systems biology: lessons from a single-gene circuit | 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 Article Simplifications and approximations in molecular systems biology: lessons from a single-gene circuit Luis Diambra, Alejandro Barton, Pablo Sesin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3911963/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract The absence of detailed knowledge about regulatory interactions makes the use of phenomenological assumptions mandatory in cell biology modeling. Furthermore, the challenges associated with the analysis of these models compel the implementation of mathematical approximations. However, the constraints these methods introduce to biological interpretation are sometimes neglected. Consequently, understanding these restrictions is a very important task for systems biology modeling.In this article, we examine the impact of such simplifications taking the case of a single-gene autoinhibitory circuit, however, our conclusions are not limited solely to this instance. We demonstrate that models grounded in the same biological assumptions but described at varying levels of detail can lead to different outcomes, that is different and contradictory phenotypes or behaviors. Indeed, incorporating specific molecular processes like translation and elongation into the model can introduce instabilities and oscillations not seen when these processes are assumed to be instantaneous. Furthermore, incorporating a detailed description of promoter dynamics, usually described by a phenomenological regulatory function, can lead to instability depending on the cooperative binding mechanism that is acting. Consequently, although the use of a regulating function facilitates model analysis, it may mask relevant aspects of the system's behavior. In particular, we observe that the two cooperative binding mechanisms, both compatible with the same sigmoidal function, can lead to different phenotypes, such as transcriptional oscillations with different frequencies. Biological sciences/Systems biology Biological sciences/Systems biology/Biochemical networks Biological sciences/Systems biology/Control theory Biological sciences/Systems biology/Genetic circuit engineering Biological sciences/Systems biology/Nonlinear dynamics Biological sciences/Systems biology/Oscillators Biological sciences/Systems biology/Regulatory networks Physical sciences/Physics/Biological physics Physical sciences/Physics/Statistical physics thermodynamics and nonlinear dynamics Full Text Additional Declarations No competing interests reported. Supplementary Files suppmat.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 25 Apr, 2024 Reviews received at journal 13 Apr, 2024 Reviews received at journal 22 Mar, 2024 Reviewers agreed at journal 21 Mar, 2024 Reviewers agreed at journal 11 Mar, 2024 Reviewers agreed at journal 08 Mar, 2024 Reviewers invited by journal 07 Mar, 2024 Editor assigned by journal 06 Mar, 2024 Editor invited by journal 27 Feb, 2024 Submission checks completed at journal 27 Feb, 2024 First submitted to journal 30 Jan, 2024 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-3911963","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":275193543,"identity":"52f62b79-4acb-4d89-91e7-668bb846ba34","order_by":0,"name":"Luis Diambra","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBACPobEBgbGBgYGfhAvoYAILWwwLZINIC0GRGlJYABrMTgA4hKlhT258dPNHffkjc+vTvzwwIBBnl/sAAEtPA+bpXPPFBtuu/F2swTQYYYzZycQ0CKR2CCd25bAuO3G2Q0gLQkGtwlraf4N1GK/ecbZzT+I1dIGsiVxA3/vNiJt4XnYZp17JiF5xg3ebRYJBhKE/cLPnv74du6OBNv+/rObb/6osJHnlyagBQEkwColiFUOtu8AKapHwSgYBaNgJAEAKFtGBlL2R4wAAAAASUVORK5CYII=","orcid":"","institution":"National University of La Plata","correspondingAuthor":true,"prefix":"","firstName":"Luis","middleName":"","lastName":"Diambra","suffix":""},{"id":275193544,"identity":"c88f8fe9-c535-4e2b-9cdf-77f597bf5723","order_by":1,"name":"Alejandro Barton","email":"","orcid":"","institution":"National University of La Plata","correspondingAuthor":false,"prefix":"","firstName":"Alejandro","middleName":"","lastName":"Barton","suffix":""},{"id":275193545,"identity":"2a0e9908-3d95-4009-a8dd-b2ff674b5ec3","order_by":2,"name":"Pablo Sesin","email":"","orcid":"","institution":"Comisión Nacional de Energía Atómica","correspondingAuthor":false,"prefix":"","firstName":"Pablo","middleName":"","lastName":"Sesin","suffix":""}],"badges":[],"createdAt":"2024-01-30 23:44:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3911963/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3911963/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51969414,"identity":"a9b2def3-595b-46ca-a12d-b36f946d4af5","added_by":"auto","created_at":"2024-03-04 18:40:19","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":725966,"visible":true,"origin":"","legend":"","description":"","filename":"oscidelay.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3911963/v1_covered_b970c4f9-9c2d-424c-850e-9db104df36d5.pdf"},{"id":51967876,"identity":"9ef2a377-6364-43ee-8a31-7f398987014c","added_by":"auto","created_at":"2024-03-04 18:32:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":154972,"visible":true,"origin":"","legend":"","description":"","filename":"suppmat.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3911963/v1/90db04736f5204d4f5f26435.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Simplifications and approximations in molecular systems biology: lessons from a single-gene circuit","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3911963/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3911963/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"The absence of detailed knowledge about regulatory interactions makes the use of phenomenological assumptions mandatory in cell biology modeling. 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