Transcriptional and Proteomic Network Integration in Response to Structured Acoustic Stimulation: A Computational Mediation Model

Transcriptional and Proteomic Network Integration in Response to Structured Acoustic Stimulation: A Computational Mediation Model | 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 Transcriptional and Proteomic Network Integration in Response to Structured Acoustic Stimulation: A Computational Mediation Model SONALI MOHAN This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8975470/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 Acoustic stimulation has been shown to influence neural activity and physiological states, yet its systems-level molecular integration remains poorly characterized. Here, we present a computational mediation model integrating transcriptional and proteomic network dynamics in response to a structurally defined mantra-derived acoustic stimulus. The framework models hierarchical coupling between activity-dependent transcriptional regulators, mitochondrial bioenergetic pathways, and inflammatory signaling modules. Simulated multi-omics integration predicts coordinated activation of CREB-associated gene networks, PGC-1α–mediated mitochondrial biogenesis, and Nrf2-dependent redox stabilization, alongside attenuation of NF-κB–regulated inflammatory cascades. Network modularity analysis identifies convergent regulatory hubs linking transcriptional activation to downstream proteomic stabilization. Mediation modeling further suggests that bioenergetic pathway engagement partially mediates the relationship between transcriptional activation and global network efficiency. Collectively, this systems-biology framework proposes a mechanistic architecture through which structured acoustic stimulation may influence cellular resilience. The model generates experimentally testable predictions for multi-omics validation and provides a quantitative foundation for studying sound-induced molecular network adaptation. Computational Neuroscience Cellular & Molecular Neuroscience Structured acoustic stimulation Systems biology Multi-omics integration CREB signaling Neuroplasticity Mitochondrial biogenesis Nrf2 pathway NF-κB suppression Hormesis Computational modeling Full Text Additional Declarations The authors declare no competing interests. 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-8975470","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":597848808,"identity":"6f316e71-7431-447e-81fd-b860dc1ef0bd","order_by":0,"name":"SONALI MOHAN","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBElEQVRIiWNgGAWjYBAC+QYg8cCAgQGIGB9+qLABchkbD+DTYgCSTYBoYTaWOJMG0tKAXwuISIAw2CR4Ww6DRfFrYe89+CGhYJucOfvZAxKSDeft1rYfBtpSYxON0y8955IlEgxuG1v25CUYFO64nbztTCJQy7G03AZcem7kGIC0JG44kGOQIHnmdrLZAaAWxobD+LQY/wBrOf/G4ABv27lks/MPCWoxg9hyI8ewgbftgJ3ZDQK2GJw5Y2YB8ovBjTfGzBJnkhPMbgBtScDjF/n2HuMbH/7cljM4n2P+80OFnb3Z+fSHDz7U2OB2GDpIBKtMIFY5CNiTongUjIJRMApGBgAASqhr9O6LJ6oAAAAASUVORK5CYII=","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"SONALI","middleName":"","lastName":"MOHAN","suffix":""}],"badges":[],"createdAt":"2026-02-26 08:42:01","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8975470/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8975470/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104399940,"identity":"6a6ba3aa-ac35-41a7-8982-1ca7fc7a759c","added_by":"auto","created_at":"2026-03-11 12:08:15","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":469448,"visible":true,"origin":"","legend":"","description":"","filename":"2026CPJune3MBCCTranscriptionalandProteomicNetworkIntegrationinResponsetoStructuredAcousticStimulationAComputationalMediationModel.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8975470/v1_covered_79777d3e-7c34-4e14-a464-d0d18eaf9c01.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eTranscriptional and Proteomic Network Integration in Response to Structured Acoustic Stimulation: A Computational Mediation Model\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"INDEPENDENT RESEARCHER ","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Structured acoustic stimulation, Systems biology, Multi-omics integration, CREB signaling, Neuroplasticity, Mitochondrial biogenesis, Nrf2 pathway, NF-κB suppression, Hormesis, Computational modeling","lastPublishedDoi":"10.21203/rs.3.rs-8975470/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8975470/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAcoustic stimulation has been shown to influence neural activity and physiological states, yet its systems-level molecular integration remains poorly characterized. Here, we present a computational mediation model integrating transcriptional and proteomic network dynamics in response to a structurally defined mantra-derived acoustic stimulus. The framework models hierarchical coupling between activity-dependent transcriptional regulators, mitochondrial bioenergetic pathways, and inflammatory signaling modules. Simulated multi-omics integration predicts coordinated activation of CREB-associated gene networks, PGC-1α–mediated mitochondrial biogenesis, and Nrf2-dependent redox stabilization, alongside attenuation of NF-κB–regulated inflammatory cascades. Network modularity analysis identifies convergent regulatory hubs linking transcriptional activation to downstream proteomic stabilization. Mediation modeling further suggests that bioenergetic pathway engagement partially mediates the relationship between transcriptional activation and global network efficiency. Collectively, this systems-biology framework proposes a mechanistic architecture through which structured acoustic stimulation may influence cellular resilience. The model generates experimentally testable predictions for multi-omics validation and provides a quantitative foundation for studying sound-induced molecular network adaptation.\u003c/p\u003e","manuscriptTitle":"Transcriptional and Proteomic Network Integration in Response to Structured Acoustic Stimulation: A Computational Mediation Model","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-02 12:01:56","doi":"10.21203/rs.3.rs-8975470/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"29e4f882-58c5-4a57-aadc-dff39f8add00","owner":[],"postedDate":"March 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":63621538,"name":"Computational Neuroscience"},{"id":63621539,"name":"Cellular \u0026 Molecular Neuroscience"}],"tags":[],"updatedAt":"2026-03-02T12:01:56+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-02 12:01:56","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8975470","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8975470","identity":"rs-8975470","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}