Target rule exploration of drug combination based on directed weighted network

Target rule exploration of drug combination based on directed weighted network | 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 Target rule exploration of drug combination based on directed weighted network Jinwei Bai, Rongwu Xiang, Yuhang Li, Zhenhua Shen, Can Huang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4831740/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 Background In the realm of drug discovery, deciphering the interaction rules of drug combinations at the target level within biological networks is pivotal for developing effective therapeutic strategies. This study introduces a novel method for identifying drug combinations using a directed weighted network model. This model is developed by analyzing drug-directed information, target-directed information, and potential dynamic global changes in drug action within the network. Results By leveraging network topology relationships, the target regularity of drug combinations is investigated, and a corresponding discriminant algorithm is designed. Comparative analysis with existing models demonstrates the superior prediction accuracy of our approach. The results highlight the efficacy of our method in identifying various types of drug combinations, bridging the gap between current research on biological network-based drug combinations and actual drug action information. Furthermore, our approach reveals potential synergistic or antagonistic mechanisms underlying these combinations, providing valuable insights for the development of combination therapies. Conclusions Our findings confirm that the proposed method effectively identifies different types of drug combinations and provides a deeper understanding of the mechanisms behind these combinations. The study offers a robust tool for the rational design of drug combinations, potentially enhancing therapeutic efficacy and reducing adverse effects. drug combination directed weighted network drug combination discrimination mechanism of action target regularity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Full Text Additional Declarations No competing interests reported. Supplementary Files 1.xlsx 2.xlsx 3.xlsx 4.xlsx 5.xlsx 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. 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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-4831740","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":339152189,"identity":"ebe3c38c-e94f-4d24-88a3-743b4f17b4d5","order_by":0,"name":"Jinwei Bai","email":"","orcid":"","institution":"Shenyang Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Jinwei","middleName":"","lastName":"Bai","suffix":""},{"id":339152190,"identity":"9474798e-cf1f-4d94-88bc-efa6a0b1617e","order_by":1,"name":"Rongwu Xiang","email":"","orcid":"","institution":"Shenyang Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Rongwu","middleName":"","lastName":"Xiang","suffix":""},{"id":339152191,"identity":"77e35066-8372-45db-b571-bdfe574b70fb","order_by":2,"name":"Yuhang Li","email":"","orcid":"","institution":"Shenyang Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Yuhang","middleName":"","lastName":"Li","suffix":""},{"id":339152192,"identity":"bd6de42b-d83a-4a89-aef1-c59e2cc26604","order_by":3,"name":"Zhenhua Shen","email":"","orcid":"","institution":"Shenyang Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Zhenhua","middleName":"","lastName":"Shen","suffix":""},{"id":339152193,"identity":"a96ee619-3838-4240-9bb5-8947db83acf8","order_by":4,"name":"Can Huang","email":"","orcid":"","institution":"Shenyang Pharmaceutical University","correspondingAuthor":false,"prefix":"","firstName":"Can","middleName":"","lastName":"Huang","suffix":""},{"id":339152194,"identity":"dbbd97d2-6850-43fa-971f-027829923376","order_by":5,"name":"Shen Xiao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYBACNmbmAwc/GEjwyLM3MDAwNoDEEvBr4WNvS3wsUWEhY9hzgEgtcjxnlA14zlTYMNxIIFILm0QOm4RkmwQP48znz6QLdxxm4GfPMWD4uQOfltxjEoVALezSOWbSM88cZpDseWPA2HsGn5a8NIgts3PYpHnbDjMY3MgxYGZsw+swMwleoBaGm8efgbXYE9TCc8YY6H2glhsMZhBbJAhpgQSyBI9hT46x9cy2dB6JM88KDvbi0SLfDI7KOnt59uMPbxe2WcvxtydvfPATjxZkwCINJHhArAPEaWBgYP5MrMpRMApGwSgYWQAAG9pLWfbpH98AAAAASUVORK5CYII=","orcid":"","institution":"Shenyang Pharmaceutical University","correspondingAuthor":true,"prefix":"","firstName":"Shen","middleName":"","lastName":"Xiao","suffix":""}],"badges":[],"createdAt":"2024-07-31 02:06:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4831740/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4831740/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63452926,"identity":"6793661f-203f-4cc1-bcc5-40acea1d344e","added_by":"auto","created_at":"2024-08-28 09:43:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1021034,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of targets network. (A) Target directed network; (B) Directed weighted network of drug combination target.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/a5e32f7b6e8f0a4be9e3b7df.png"},{"id":63451464,"identity":"d805522c-26de-41f5-a571-26cf6c75a420","added_by":"auto","created_at":"2024-08-28 09:27:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":282553,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of indirect target acquisition.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/3748989e7ea7bb9796efaadf.png"},{"id":63451479,"identity":"2d25e56f-1dbb-4152-bd17-7edf36b1f158","added_by":"auto","created_at":"2024-08-28 09:27:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":372357,"visible":true,"origin":"","legend":"\u003cp\u003eDiscriminant accuracy of drug combination under different attenuation coefficients\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/e88a735b737bad91a2865257.png"},{"id":63451471,"identity":"39017fc3-7e46-42aa-92e5-d1674bef921e","added_by":"auto","created_at":"2024-08-28 09:27:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1015638,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of network-based drug combination interaction effects.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/65788fe62af1082522c25821.png"},{"id":63451971,"identity":"f683438c-0fbe-4d2d-bda6-74700c37e027","added_by":"auto","created_at":"2024-08-28 09:35:18","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":450326,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of drug combination target distance.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/f03345a32ac51ca1f65b587a.png"},{"id":63451467,"identity":"674496d1-250f-4cd8-8eeb-a7ee15f2fb32","added_by":"auto","created_at":"2024-08-28 09:27:18","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":704009,"visible":true,"origin":"","legend":"\u003cp\u003eDrug combination network topology relationship.\u003c/p\u003e","description":"","filename":"image6.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/90dd803e1bbee2afeccb43e7.png"},{"id":63451968,"identity":"25e4ceb1-2225-4006-aa0d-042617d70928","added_by":"auto","created_at":"2024-08-28 09:35:18","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":607327,"visible":true,"origin":"","legend":"\u003cp\u003eMethod Overall process. (A) Data collection; (B) Construction of directed weighted network; (C) Calculation of network distance between drug combination target sets; (D) Identification of drug combination types.\u003c/p\u003e","description":"","filename":"image7.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/2ea99da667315eed4e6823e1.png"},{"id":63453565,"identity":"7b34b29c-4d64-4d1b-b1db-0293462b5bfc","added_by":"auto","created_at":"2024-08-28 09:51:18","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":1239772,"visible":true,"origin":"","legend":"\u003cp\u003eDirected weighted network of synergistic-7. Synergistic drug combinations represent network\u003c/p\u003e","description":"","filename":"image8.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/6242b2318928c2640055a9fd.png"},{"id":63451977,"identity":"07cb6131-41c8-43a7-9806-4ea20c193f79","added_by":"auto","created_at":"2024-08-28 09:35:19","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":1070421,"visible":true,"origin":"","legend":"\u003cp\u003eDirected weighted network of antagonistic-5. Antagonistic drug combinations represent network\u003c/p\u003e","description":"","filename":"image9.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/58eaf1b0afa3e0502abab149.png"},{"id":63451477,"identity":"fbeda4cc-6d88-42bb-8a03-544116bd4e4c","added_by":"auto","created_at":"2024-08-28 09:27:18","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":1390464,"visible":true,"origin":"","legend":"\u003cp\u003eDrug combination network topology relationship. (A) Synergistic drug combination network topology (d+\u0026lt;0, d-\u0026lt;0); (B) Antagonistic drug combination network topology (d+\u0026gt;0, d-\u0026lt;0); (C) Antagonistic drug combination network topology (d+\u0026lt;0, d-\u0026gt;0); (D) Antagonistic drug combination network topology (d+\u0026gt;0, d-\u0026gt;0).\u003c/p\u003e","description":"","filename":"image10.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/c7509c2ce0a4d6c1ccec0664.png"},{"id":63451472,"identity":"4d8c79e9-96a8-4d50-bbbc-b39288cfd6b5","added_by":"auto","created_at":"2024-08-28 09:27:18","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":80858,"visible":true,"origin":"","legend":"\u003cp\u003eDrug combination d value distribution\u003c/p\u003e","description":"","filename":"image11.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/5e79b509ae0671897f6fb8e3.png"},{"id":63451480,"identity":"71e057c0-c835-4eb0-98c3-33388d17d2aa","added_by":"auto","created_at":"2024-08-28 09:27:19","extension":"png","order_by":12,"title":"Figure 12","display":"","copyAsset":false,"role":"figure","size":264854,"visible":true,"origin":"","legend":"\u003cp\u003eIntersection of drug combinations and corresponding symptomatic targets\u003c/p\u003e","description":"","filename":"image12.png","url":"https://assets-eu.researchsquare.com/files/rs-4831740/v1/d3276c1df8e210caa1e206aa.png"},{"id":71754683,"identity":"adb8f1b6-a370-4fc2-87ed-5e6779780fae","added_by":"auto","created_at":"2024-12-18 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network","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","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":"drug combination, directed weighted network, drug combination discrimination, mechanism of action, target regularity","lastPublishedDoi":"10.21203/rs.3.rs-4831740/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4831740/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn the realm of drug discovery, deciphering the interaction rules of drug combinations at the target level within biological networks is pivotal for developing effective therapeutic strategies. This study introduces a novel method for identifying drug combinations using a directed weighted network model. This model is developed by analyzing drug-directed information, target-directed information, and potential dynamic global changes in drug action within the network.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBy leveraging network topology relationships, the target regularity of drug combinations is investigated, and a corresponding discriminant algorithm is designed. Comparative analysis with existing models demonstrates the superior prediction accuracy of our approach. The results highlight the efficacy of our method in identifying various types of drug combinations, bridging the gap between current research on biological network-based drug combinations and actual drug action information. Furthermore, our approach reveals potential synergistic or antagonistic mechanisms underlying these combinations, providing valuable insights for the development of combination therapies.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOur findings confirm that the proposed method effectively identifies different types of drug combinations and provides a deeper understanding of the mechanisms behind these combinations. The study offers a robust tool for the rational design of drug combinations, potentially enhancing therapeutic efficacy and reducing adverse effects.\u003c/p\u003e","manuscriptTitle":"Target rule exploration of drug combination based on directed weighted network","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-28 09:27:13","doi":"10.21203/rs.3.rs-4831740/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":"1a4fafaf-074f-4858-bd7b-c2cdce9e5536","owner":[],"postedDate":"August 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-18T09:53:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-28 09:27:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4831740","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4831740","identity":"rs-4831740","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}