IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36637-3.html
   My bibliography  Save this article

ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs

Author

Listed:
  • Bing He

    (University of Michigan)

  • Yao Xiao

    (University of Michigan)

  • Haodong Liang

    (University of Michigan)

  • Qianhui Huang

    (University of Michigan)

  • Yuheng Du

    (University of Michigan)

  • Yijun Li

    (University of Michigan)

  • David Garmire

    (University of Michigan)

  • Duxin Sun

    (University of Michigan)

  • Lana X. Garmire

    (University of Michigan)

Abstract

Single-cell RNA sequencing technology has enabled in-depth analysis of intercellular heterogeneity in various diseases. However, its full potential for precision medicine has yet to be reached. Towards this, we propose A Single-cell Guided Pipeline to Aid Repurposing of Drugs (ASGARD) that defines a drug score to recommend drugs by considering all cell clusters to address the intercellular heterogeneity within each patient. ASGARD shows significantly better average accuracy on single-drug therapy compared to two bulk-cell-based drug repurposing methods. We also demonstrated that it performs considerably better than other cell cluster-level predicting methods. In addition, we validate ASGARD using the drug response prediction method TRANSACT with Triple-Negative-Breast-Cancer patient samples. We find that many top-ranked drugs are either approved by the Food and Drug Administration or in clinical trials treating corresponding diseases. In conclusion, ASGARD is a promising drug repurposing recommendation tool guided by single-cell RNA-seq for personalized medicine. ASGARD is free for educational use at https://github.com/lanagarmire/ASGARD .

Suggested Citation

  • Bing He & Yao Xiao & Haodong Liang & Qianhui Huang & Yuheng Du & Yijun Li & David Garmire & Duxin Sun & Lana X. Garmire, 2023. "ASGARD is A Single-cell Guided Pipeline to Aid Repurposing of Drugs," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36637-3
    DOI: 10.1038/s41467-023-36637-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36637-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36637-3?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. Bojan Losic & Amanda J. Craig & Carlos Villacorta-Martin & Sebastiao N. Martins-Filho & Nicholas Akers & Xintong Chen & Mehmet E. Ahsen & Johann Felden & Ismail Labgaa & Delia DʹAvola & Kimaada Allett, 2020. "Intratumoral heterogeneity and clonal evolution in liver cancer," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    2. Jordan W. Squair & Matthieu Gautier & Claudia Kathe & Mark A. Anderson & Nicholas D. James & Thomas H. Hutson & Rémi Hudelle & Taha Qaiser & Kaya J. E. Matson & Quentin Barraud & Ariel J. Levine & Gio, 2021. "Confronting false discoveries in single-cell differential expression," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. D. Merino & T. S. Weber & A. Serrano & F. Vaillant & K. Liu & B. Pal & L. Stefano & J. Schreuder & D. Lin & Y. Chen & M. L. Asselin-Labat & T. N. Schumacher & D. Cameron & G. K. Smyth & A. T. Papenfus, 2019. "Publisher Correction: Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer," Nature Communications, Nature, vol. 10(1), pages 1-2, December.
    4. L. Vanderbeke & P. Van Mol & Y. Van Herck & F. De Smet & S. Humblet-Baron & K. Martinod & A. Antoranz & I. Arijs & B. Boeckx & F. M. Bosisio & M. Casaer & D. Dauwe & W. De Wever & C. Dooms & E. Dreese, 2021. "Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. D. Merino & T. S. Weber & A. Serrano & F. Vaillant & K. Liu & B. Pal & L. Stefano & J. Schreuder & D. Lin & Y. Chen & M. L. Asselin-Labat & T. N. Schumacher & D. Cameron & G. K. Smyth & A. T. Papenfus, 2019. "Barcoding reveals complex clonal behavior in patient-derived xenografts of metastatic triple negative breast cancer," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    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. Humberto Contreras-Trujillo & Jiya Eerdeng & Samir Akre & Du Jiang & Jorge Contreras & Basia Gala & Mary C. Vergel-Rodriguez & Yeachan Lee & Aparna Jorapur & Areen Andreasian & Lisa Harton & Charles S, 2021. "Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Louise A. Baldwin & Nenad Bartonicek & Jessica Yang & Sunny Z. Wu & Niantao Deng & Daniel L. Roden & Chia-Ling Chan & Ghamdan Al-Eryani & Damien J. Zanker & Belinda S. Parker & Alexander Swarbrick & S, 2022. "DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and immunotherapy response," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Peter Eirew & Ciara O’Flanagan & Jerome Ting & Sohrab Salehi & Jazmine Brimhall & Beixi Wang & Justina Biele & Teresa Algara & So Ra Lee & Corey Hoang & Damian Yap & Steven McKinney & Cherie Bates & E, 2022. "Accurate determination of CRISPR-mediated gene fitness in transplantable tumours," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Qiuchen Guo & Milos Spasic & Adam G. Maynard & Gregory J. Goreczny & Amanuel Bizuayehu & Jessica F. Olive & Peter Galen & Sandra S. McAllister, 2022. "Clonal barcoding with qPCR detection enables live cell functional analyses for cancer research," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Raymond Hall Yip Louie & Curtis Cai & Jerome Samir & Mandeep Singh & Ira W. Deveson & James M. Ferguson & Timothy G. Amos & Helen Marie McGuire & Kavitha Gowrishankar & Thiruni Adikari & Robert Balder, 2023. "CAR+ and CAR− T cells share a differentiation trajectory into an NK-like subset after CD19 CAR T cell infusion in patients with B cell malignancies," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Manvendra Singh & Ying Zhao & Vinicius Daguano Gastaldi & Sonja M. Wojcik & Yasmina Curto & Riki Kawaguchi & Ricardo M. Merino & Laura Fernandez Garcia-Agudo & Holger Taschenberger & Nils Brose & Dani, 2023. "Erythropoietin re-wires cognition-associated transcriptional networks," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Jakob Ankerhold & Sebastian Giese & Philipp Kolb & Andrea Maul-Pavicic & Reinhard E. Voll & Nathalie Göppert & Kevin Ciminski & Clemens Kreutz & Achim Lother & Ulrich Salzer & Wolfgang Bildl & Tim Wel, 2022. "Circulating multimeric immune complexes contribute to immunopathology in COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    9. Suhas V. Vasaikar & Adam K. Savage & Qiuyu Gong & Elliott Swanson & Aarthi Talla & Cara Lord & Alexander T. Heubeck & Julian Reading & Lucas T. Graybuck & Paul Meijer & Troy R. Torgerson & Peter J. Sk, 2023. "A comprehensive platform for analyzing longitudinal multi-omics data," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Alan E. Murphy & Nathan G. Skene, 2022. "A balanced measure shows superior performance of pseudobulk methods in single-cell RNA-sequencing analysis," Nature Communications, Nature, vol. 13(1), pages 1-4, December.
    11. Zhenzhen Chen & Qiankun He & Tiankun Lu & Jiayi Wu & Gaoli Shi & Luyun He & Hong Zong & Benyu Liu & Pingping Zhu, 2023. "mcPGK1-dependent mitochondrial import of PGK1 promotes metabolic reprogramming and self-renewal of liver TICs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Zhu, Guang & Lin, Zhenhua, 2021. "Commentary on statistical mechanical models of cancer," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 572(C).
    13. Jia-Ru Wei & Zhao-Zhe Hao & Chuan Xu & Mengyao Huang & Lei Tang & Nana Xu & Ruifeng Liu & Yuhui Shen & Sarah A. Teichmann & Zhichao Miao & Sheng Liu, 2022. "Identification of visual cortex cell types and species differences using single-cell RNA sequencing," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    14. David G. Coffey & Francesco Maura & Edgar Gonzalez-Kozlova & J. Javier Diaz-Mejia & Ping Luo & Yong Zhang & Yuexin Xu & Edus H. Warren & Travis Dawson & Brian Lee & Hui Xie & Eric Smith & Amanda Ciard, 2023. "Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    15. Jonas Stewen & Kai Kruse & Anca T. Godoi-Filip & Zenia & Hyun-Woo Jeong & Susanne Adams & Frank Berkenfeld & Martin Stehling & Kristy Red-Horse & Ralf H. Adams & Mara E. Pitulescu, 2024. "Eph-ephrin signaling couples endothelial cell sorting and arterial specification," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    16. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Manon Venet & Margarida Sa Ribeiro & Elodie Décembre & Alicia Bellomo & Garima Joshi & Célia Nuovo & Marine Villard & David Cluet & Magali Perret & Rémi Pescamona & Helena Paidassi & Thierry Walzer & , 2023. "Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    18. BaDoi N. Phan & Madelyn H. Ray & Xiangning Xue & Chen Fu & Robert J. Fenster & Stephen J. Kohut & Jack Bergman & Suzanne N. Haber & Kenneth M. McCullough & Madeline K. Fish & Jill R. Glausier & Qiao S, 2024. "Single nuclei transcriptomics in human and non-human primate striatum in opioid use disorder," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    19. Hai C. T. Nguyen & Bukyung Baik & Sora Yoon & Taesung Park & Dougu Nam, 2023. "Benchmarking integration of single-cell differential expression," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Eloise Berson & Anjali Sreenivas & Thanaphong Phongpreecha & Amalia Perna & Fiorella C. Grandi & Lei Xue & Neal G. Ravindra & Neelufar Payrovnaziri & Samson Mataraso & Yeasul Kim & Camilo Espinosa & A, 2023. "Whole genome deconvolution unveils Alzheimer’s resilient epigenetic signature," Nature Communications, Nature, vol. 14(1), pages 1-11, 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:14:y:2023:i:1:d:10.1038_s41467-023-36637-3. 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.