Modeling Brain Metabolism through Calculus/Statistical Isotopic Tracing: A Cost-Efficient Predictive Framework

Modeling Brain Metabolism through Calculus/Statistical Isotopic Tracing: A Cost-Efficient Predictive Framework | 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 Method Article Modeling Brain Metabolism through Calculus/Statistical Isotopic Tracing: A Cost-Efficient Predictive Framework Akhil Shunmugaraja This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8310360/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Isotopic tracing is a process in which metabolites are labeled with isotopes that can be tracked throughout specific cellular processes( 1 ). An isotope is a version of a chemical that has the same number of protons and electrons, but differs in its neutron composition. This process works by substituting molecules with isotopes and monitoring their movement through systems over time. Because isotopes behave like their parent molecules but differ in mass, tracing them is feasible and reveals each molecule’s role in a system. However, determining the precise entry rate for labeled metabolites is challenging. The use of heavier isotopes makes reactions appear slower than they actually are, because they do not form/break bonds as readily. This phenomenon, Mass-Dependent Fractionation (MDF), causes measurements to underestimate the true reaction rate in a system. In a system that is as fast as brain metabolism, these issues can lead to falsified data. After experimentation, it was concluded that through mathematical applications in isotopic tracing models, the rate of entry can be accurately predicted, strengthening in vivo data. By doing so, the progression of isotopic labeling can be predicted without the influence of MDF bias. To test this, brain metabolism was modeled with sticky notes, with different colors modeling two carbon isotopes. Patterns were observed and analyzed as the experiment ran under numerous scenarios. This study demonstrates that using simple calculus to generate models enables preliminary experiment analysis, allowing researchers to compare observed results with model predictions, and control for potential MDF bias. Biomedical Engineering Mathematical and Theoretical Biology Systems Biology Mass-Dependant Fractionation Isotopes Isotopic Tracing Brain metabolism calculus Full Text Additional Declarations The authors declare no competing interests. Supplementary Files IsometricTracingGraph.xlsx Data from Experiment 1 2.xlsx Data from Experiment 2 StatisticalBarGraphswErrorBars.xlsx Overall statistic relationships among the three experiments 3.xlsx Data from Experiment 3 Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8310360","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Method Article","associatedPublications":[],"authors":[{"id":557183301,"identity":"8f2b8012-1278-43e4-b92f-0b72dac388eb","order_by":0,"name":"Akhil 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An isotope is a version of a chemical that has the same number of protons and electrons, but differs in its neutron composition. This process works by substituting molecules with isotopes and monitoring their movement through systems over time. Because isotopes behave like their parent molecules but differ in mass, tracing them is feasible and reveals each molecule\u0026rsquo;s role in a system. However, determining the precise entry rate for labeled metabolites is challenging. The use of heavier isotopes makes reactions appear slower than they actually are, because they do not form/break bonds as readily. This phenomenon, Mass-Dependent Fractionation (MDF), causes measurements to underestimate the true reaction rate in a system. In a system that is as fast as brain metabolism, these issues can lead to falsified data. 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