IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-021-27751-1.html
   My bibliography  Save this article

Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension

Author

Listed:
  • Patrick Wu

    (Vanderbilt University Medical Center
    Vanderbilt University School of Medicine)

  • QiPing Feng

    (Vanderbilt University Medical Center)

  • Vern Eric Kerchberger

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Scott D. Nelson

    (Vanderbilt University Medical Center)

  • Qingxia Chen

    (Vanderbilt University Medical Center
    Vanderbilt University School of Medicine)

  • Bingshan Li

    (Vanderbilt University School of Medicine
    Vanderbilt University Medical Center)

  • Todd L. Edwards

    (Vanderbilt University Medical Center
    Tennessee Valley Healthcare System (626)/Vanderbilt University
    Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Nancy J. Cox

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Elizabeth J. Phillips

    (Vanderbilt University Medical Center
    Vanderbilt University School of Medicine
    Vanderbilt University Medical Center
    Murdoch University)

  • C. Michael Stein

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center
    Vanderbilt University School of Medicine)

  • Dan M. Roden

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center
    Vanderbilt University School of Medicine)

  • Joshua C. Denny

    (National Institutes of Health
    National Institutes of Health)

  • Wei-Qi Wei

    (Vanderbilt University Medical Center)

Abstract

Discovering novel uses for existing drugs, through drug repurposing, can reduce the time, costs, and risk of failure associated with new drug development. However, prioritizing drug repurposing candidates for downstream studies remains challenging. Here, we present a high-throughput approach to identify and validate drug repurposing candidates. This approach integrates human gene expression, drug perturbation, and clinical data from publicly available resources. We apply this approach to find drug repurposing candidates for two diseases, hyperlipidemia and hypertension. We screen >21,000 compounds and replicate ten approved drugs. We also identify 25 (seven for hyperlipidemia, eighteen for hypertension) drugs approved for other indications with therapeutic effects on clinically relevant biomarkers. For five of these drugs, the therapeutic effects are replicated in the All of Us Research Program database. We anticipate our approach will enable researchers to integrate multiple publicly available datasets to identify high priority drug repurposing opportunities for human diseases.

Suggested Citation

  • Patrick Wu & QiPing Feng & Vern Eric Kerchberger & Scott D. Nelson & Qingxia Chen & Bingshan Li & Todd L. Edwards & Nancy J. Cox & Elizabeth J. Phillips & C. Michael Stein & Dan M. Roden & Joshua C. D, 2022. "Integrating gene expression and clinical data to identify drug repurposing candidates for hyperlipidemia and hypertension," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27751-1
    DOI: 10.1038/s41467-021-27751-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-27751-1
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-021-27751-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Dorothée Diogo & Chao Tian & Christopher S. Franklin & Mervi Alanne-Kinnunen & Michael March & Chris C. A. Spencer & Ciara Vangjeli & Michael E. Weale & Hannele Mattsson & Elina Kilpeläinen & Patrick , 2018. "Phenome-wide association studies across large population cohorts support drug target validation," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    2. Yukinori Okada & Di Wu & Gosia Trynka & Towfique Raj & Chikashi Terao & Katsunori Ikari & Yuta Kochi & Koichiro Ohmura & Akari Suzuki & Shinji Yoshida & Robert R. Graham & Arun Manoharan & Ward Ortman, 2014. "Genetics of rheumatoid arthritis contributes to biology and drug discovery," Nature, Nature, vol. 506(7488), pages 376-381, February.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xiaoguang Xu & Chachrit Khunsriraksakul & James M. Eales & Sebastien Rubin & David Scannali & Sushant Saluja & David Talavera & Havell Markus & Lida Wang & Maciej Drzal & Akhlaq Maan & Abigail C. Lay , 2024. "Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets," Nature Communications, Nature, vol. 15(1), pages 1-29, December.
    2. Marcin Pilarczyk & Mehdi Fazel-Najafabadi & Michal Kouril & Behrouz Shamsaei & Juozas Vasiliauskas & Wen Niu & Naim Mahi & Lixia Zhang & Nicholas A. Clark & Yan Ren & Shana White & Rashid Karim & Huan, 2022. "Connecting omics signatures and revealing biological mechanisms with iLINCS," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Pietro Demela & Nicola Pirastu & Blagoje Soskic, 2023. "Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Mary-Ellen Lynall & Blagoje Soskic & James Hayhurst & Jeremy Schwartzentruber & Daniel F. Levey & Gita A. Pathak & Renato Polimanti & Joel Gelernter & Murray B. Stein & Gosia Trynka & Menna R. Clatwor, 2022. "Genetic variants associated with psychiatric disorders are enriched at epigenetically active sites in lymphoid cells," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Roy Oelen & Dylan H. Vries & Harm Brugge & M. Grace Gordon & Martijn Vochteloo & Chun J. Ye & Harm-Jan Westra & Lude Franke & Monique G. P. Wijst, 2022. "Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Guanghao Qi & Surya B. Chhetri & Debashree Ray & Diptavo Dutta & Alexis Battle & Samsiddhi Bhattacharjee & Nilanjan Chatterjee, 2024. "Genome-wide large-scale multi-trait analysis characterizes global patterns of pleiotropy and unique trait-specific variants," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Duc-Hau Le, 2021. "A network-based method for predicting disease-associated enhancers," PLOS ONE, Public Library of Science, vol. 16(12), pages 1-20, December.
    6. Feng Jiang & Shou-Ye Hu & Wen Tian & Nai-Ning Wang & Ning Yang & Shan-Shan Dong & Hui-Miao Song & Da-Jin Zhang & Hui-Wu Gao & Chen Wang & Hao Wu & Chang-Yi He & Dong-Li Zhu & Xiao-Feng Chen & Yan Guo , 2024. "A landscape of gene expression regulation for synovium in arthritis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Andrew A. Brown & Juan J. Fernandez-Tajes & Mun-gwan Hong & Caroline A. Brorsson & Robert W. Koivula & David Davtian & Théo Dupuis & Ambra Sartori & Theodora-Dafni Michalettou & Ian M. Forgie & Jonath, 2023. "Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Maik Pietzner & Eleanor Wheeler & Julia Carrasco-Zanini & Nicola D. Kerrison & Erin Oerton & Mine Koprulu & Jian’an Luan & Aroon D. Hingorani & Steve A. Williams & Nicholas J. Wareham & Claudia Langen, 2021. "Synergistic insights into human health from aptamer- and antibody-based proteomic profiling," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    9. Weikang Gong & Yan Fu & Bang-Sheng Wu & Jingnan Du & Liu Yang & Ya-Ru Zhang & Shi-Dong Chen & JuJiao Kang & Ying Mao & Qiang Dong & Lan Tan & Jianfeng Feng & Wei Cheng & Jin-Tai Yu, 2024. "Whole-exome sequencing identifies protein-coding variants associated with brain iron in 29,828 individuals," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. Kaitlyn A. Lagattuta & Hannah L. Park & Laurie Rumker & Kazuyoshi Ishigaki & Aparna Nathan & Soumya Raychaudhuri, 2024. "The genetic basis of autoimmunity seen through the lens of T cell functional traits," Nature Communications, Nature, vol. 15(1), pages 1-6, December.
    11. Thorunn A. Olafsdottir & Gudmar Thorleifsson & Aitzkoa Lopez de Lapuente Portilla & Stefan Jonsson & Lilja Stefansdottir & Abhishek Niroula & Aslaug Jonasdottir & Hannes P. Eggertsson & Gisli H. Halld, 2024. "Sequence variants influencing the regulation of serum IgG subclass levels," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    12. Taehyeung Kim & Marta Martínez-Bonet & Qiang Wang & Nicolaj Hackert & Jeffrey A. Sparks & Yuriy Baglaenko & Byunghee Koh & Roxane Darbousset & Raquel Laza-Briviesca & Xiaoting Chen & Vitor R. C. Aguia, 2024. "Non-coding autoimmune risk variant defines role for ICOS in T peripheral helper cell development," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    13. Mike Thompson & Mary Grace Gordon & Andrew Lu & Anchit Tandon & Eran Halperin & Alexander Gusev & Chun Jimmie Ye & Brunilda Balliu & Noah Zaitlen, 2022. "Multi-context genetic modeling of transcriptional regulation resolves novel disease loci," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Koen F. Dekkers & Roderick C. Slieker & Andreea Ioan-Facsinay & Maarten Iterson & M. Arfan Ikram & Marleen M. J. Greevenbroek & Jan H. Veldink & Lude Franke & Dorret I. Boomsma & P. Eline Slagboom & J, 2023. "Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    15. Clara Albiñana & Zhihong Zhu & Nis Borbye-Lorenzen & Sanne Grundvad Boelt & Arieh S. Cohen & Kristin Skogstrand & Naomi R. Wray & Joana A. Revez & Florian Privé & Liselotte V. Petersen & Cynthia M. Bu, 2023. "Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    16. James J. Gilchrist & Seiko Makino & Vivek Naranbhai & Piyush K. Sharma & Surya Koturan & Orion Tong & Chelsea A. Taylor & Robert A. Watson & Alba Verge los Aires & Rosalin Cooper & Evelyn Lau & Sara D, 2022. "Natural Killer cells demonstrate distinct eQTL and transcriptome-wide disease associations, highlighting their role in autoimmunity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27751-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.