--- title: "Synergistic drug combos from EHR & gene expression. | Sutter Health" description: "Proof-of-concept study demonstrating that EHRs and gene expression can corroborate discoveries and provide insight into drug synergism for repurposing." url: "https://www.sutterhealth.org/research/publications/synergistic-drug-combos-ehr-gene-expression-1055312518" --- 1. [Home](https://www.sutterhealth.org/) / 2. [Research](https://www.sutterhealth.org/research) / 3. [Research publications](https://www.sutterhealth.org/research/publications) / 4. Synergistic drug combos from EHR & gene expression. # Synergistic drug combinations from electronic health records and gene expression. Low YS, Daugherty AC, Schroeder EA, Chen W, Seto T, Weber S, Lim M, Hastie T, Mathur M, Desai M, Farrington C, Radin AA, Sirota M, Kenkare P, Thompson CA, Yu PP, Gomez SL, Sledge GW Jr, Kurian AW, & Shah NH. _J Am Med Inform Assoc. pii: ocw161. doi: 10.1093/jamia/ocw161. \[Epub ahead of print\]_ 2016-12-09 ## Abstract OBJECTIVE: Using electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding. METHOD: We applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis. RESULTS: From EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence. CONCLUSIONS: This is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing. [PubMed abstract](https://www.ncbi.nlm.nih.gov/pubmed/27940607) ## Research topics - [All Cancer](https://www.sutterhealth.org/research-search-results?query=%22%5C%22All+Cancer%5C%22%22) - [Medical Informatics](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Medical+Informatics%5C%22%22) - [Pharmacoepidemiology](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Pharmacoepidemiology%5C%22%22) - [Women's Health](https://www.sutterhealth.org/research-search-results?query=%22%5C%22Women%27s+Health%5C%22%22) ## Related publications [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) - Publication ### [Tradeoffs of using administrative claims and medical records to identify the use of personalized medicine for patients with breast cancer.](https://www.sutterhealth.org/research/publications/identify-use-of-personalized-med-in-breast-cancer-1055312577) Liang SY, Phillips KA, Wang G, Keohane C, Armstrong J, Morris WM, Haas JS. Med Care. 49(6):e1-8. doi: 10.1097/MLR.0b013e318207e87e. 2011 Jun 01 - Publication ### [Linking electronic health records to better understand breast cancer patient pathways within and between two health systems.](https://www.sutterhealth.org/research/publications/link-ehrs-understand-breast-cancer-pathways-1055312796) Thompson CA, Kurian AW, Luft HS. eGEMs (Generating Evidence & Methods to improve patient outcomes). 3(1). 2015 Mar 01 - Publication ### [The use of clinical characteristics to help prevent morcellation of leiomyosarcoma: An analysis of 491 cases.](https://www.sutterhealth.org/research/publications/clin-chars-prev-morcelln-lms-1055312401) Chan JK, Gardner AB, Thompson CA, Kapp DS. Am J Obstet Gynecol. 213(6):873-4. doi: 10.1016/j.ajog.2015.07.040. Epub 2015 Jul 29. 2015 Dec 01 - Publication ### [User characteristics and out-of-pocket expenditures for progestin-only versus combined oral contraceptives.](https://www.sutterhealth.org/research/publications/user-chars-expenditures-oral-contraceptives-1055312830) Liang SY, Grossman D, Phillips KA. Contraception. 86(6):666-72. doi: 10.1016/j.contraception.2012.05.018. Epub 2012 Jul 6. 2012 Dec 01 - Publication ### [Patient and provider characteristics associated with colorectal, breast, and cervical cancer screening among Asian Americans.](https://www.sutterhealth.org/research/publications/characteristics-cancer-screening-asian-american-1055312854) Thompson CA, Gomez SL, Chan A, Chan JK, McClellan SR, Chung S, Olson C, Nimbal V, Palaniappan L. Cancer Epidemiol Biomarkers Prev. 23(11):2208-17. doi: 10.1158/1055-9965.EPI-14-0487. 2014 Nov 01 [View all publications](https://www.sutterhealth.org/research-search-results?verticalKey=research_publication) ```json {"@context":"https://schema.org","@type":"MedicalOrganization","name":"Sutter Health","@id":"https://www.sutterhealth.org/#medicalorganization","url":"https://www.sutterhealth.org","logo":"https://www.sutterhealth.org/static/images/sutter-health-logo.svg","address":{"@type":"PostalAddress","streetAddress":"2200 River Plaza Drive","addressLocality":"Sacramento","addressRegion":"CA","postalCode":"95833","addressCountry":"US"},"areaServed":{"@type":"AdministrativeArea","name":"California"},"sameAs":["https://www.facebook.com/SutterHealth","https://www.instagram.com/sutterhealth/","https://x.com/SutterHealth","https://www.youtube.com/sutterhealth","https://www.linkedin.com/company/sutter-health","https://en.wikipedia.org/wiki/Sutter_Health"]} ``` ```json {"@context":"https://schema.org","@type":"BreadcrumbList","@id":"https://www.sutterhealth.org/research/publications/synergistic-drug-combos-ehr-gene-expression-1055312518#breadcrumblist","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://www.sutterhealth.org/"},{"@type":"ListItem","position":2,"name":"Research","item":"https://www.sutterhealth.org/research"},{"@type":"ListItem","position":3,"name":"Research publications","item":"https://www.sutterhealth.org/research/publications"},{"@type":"ListItem","position":4,"name":"Synergistic drug combos from EHR & gene expression."}]} ``` ```json {"@context":"https://schema.org","@type":"MedicalScholarlyArticle","@id":"https://www.sutterhealth.org/research/publications/synergistic-drug-combos-ehr-gene-expression-1055312518#medicalscholarlyarticle","name":"Synergistic drug combinations from electronic health records and gene expression.","headline":"Synergistic drug combos from EHR & gene expression.","abstract":"OBJECTIVE: Using electronic health records (EHRs) and biomolecular data, we sought to discover drug pairs with synergistic repurposing potential. EHRs provide real-world treatment and outcome patterns, while complementary biomolecular data, including disease-specific gene expression and drug-protein interactions, provide mechanistic understanding. METHOD: We applied Group Lasso INTERaction NETwork (glinternet), an overlap group lasso penalty on a logistic regression model, with pairwise interactions to identify variables and interacting drug pairs associated with reduced 5-year mortality using EHRs of 9945 breast cancer patients. We identified differentially expressed genes from 14 case-control human breast cancer gene expression datasets and integrated them with drug-protein networks. Drugs in the network were scored according to their association with breast cancer individually or in pairs. Lastly, we determined whether synergistic drug pairs found in the EHRs were enriched among synergistic drug pairs from gene-expression data using a method similar to gene set enrichment analysis. RESULTS: From EHRs, we discovered 3 drug-class pairs associated with lower mortality: anti-inflammatories and hormone antagonists, anti-inflammatories and lipid modifiers, and lipid modifiers and obstructive airway drugs. The first 2 pairs were also enriched among pairs discovered using gene expression data and are supported by molecular interactions in drug-protein networks and preclinical and epidemiologic evidence. CONCLUSIONS: This is a proof-of-concept study demonstrating that a combination of complementary data sources, such as EHRs and gene expression, can corroborate discoveries and provide mechanistic insight into drug synergism for repurposing.","description":"Proof-of-concept study demonstrating that EHRs and gene expression can corroborate discoveries and provide insight into drug synergism for repurposing.","keywords":["All Cancer","Medical Informatics","Pharmacoepidemiology","Women's Health"],"datePublished":"2016-12-09","url":"https://www.sutterhealth.org/research/publications/synergistic-drug-combos-ehr-gene-expression-1055312518","inLanguage":"en-US","identifier":[{"@type":"PropertyValue","propertyID":"PMID","value":"27940607"},{"@type":"PropertyValue","propertyID":"DOI","value":"10.1093/jamia/ocw161"}],"sameAs":["https://pubmed.ncbi.nlm.nih.gov/27940607/","https://doi.org/10.1093/jamia/ocw161"],"isPartOf":{"@type":"Periodical","name":"J Am Med Inform Assoc"},"author":[{"@type":"Person","name":"Low YS"},{"@type":"Person","name":"Daugherty AC"},{"@type":"Person","name":"Schroeder EA"},{"@type":"Person","name":"Chen W"},{"@type":"Person","name":"Seto T"},{"@type":"Person","name":"Weber S"},{"@type":"Person","name":"Lim M"},{"@type":"Person","name":"Hastie T"},{"@type":"Person","name":"Mathur M"},{"@type":"Person","name":"Desai M"},{"@type":"Person","name":"Farrington C"},{"@type":"Person","name":"Radin AA"},{"@type":"Person","name":"Sirota M"},{"@type":"Person","name":"Kenkare P"},{"@type":"Person","name":"Thompson CA"},{"@type":"Person","name":"Yu PP"},{"@type":"Person","name":"Gomez SL"},{"@type":"Person","name":"Sledge GW Jr"},{"@type":"Person","name":"Kurian AW"},{"@type":"Person","name":"Shah NH"}],"sourceOrganization":{"@type":"MedicalOrganization","name":"Palo Alto Medical Foundation Research Institute"},"about":[{"@type":"DefinedTerm","name":"All Cancer","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22All+Cancer%22%5D%7D%5D&verticalKey=research_publication"},{"@type":"DefinedTerm","name":"Medical Informatics","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Medical+Informatics%22%5D%7D%5D&verticalKey=research_publication"},{"@type":"DefinedTerm","name":"Pharmacoepidemiology","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Pharmacoepidemiology%22%5D%7D%5D&verticalKey=research_publication"},{"@type":"DefinedTerm","name":"Women's Health","url":"https://www.sutterhealth.org/research-search-results?facets=%5B%7B%22i%22%3A%22c_researchTopics.name%22%2C%22v%22%3A%5B%22Women%27s+Health%22%5D%7D%5D&verticalKey=research_publication"}],"mainEntityOfPage":{"@type":"WebPage","@id":"https://www.sutterhealth.org/research/publications/synergistic-drug-combos-ehr-gene-expression-1055312518","breadcrumb":{"@id":"https://www.sutterhealth.org/research/publications/synergistic-drug-combos-ehr-gene-expression-1055312518#breadcrumblist"}}} ```