IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52725-4.html
   My bibliography  Save this article

An automated network-based tool to search for metabolic vulnerabilities in cancer

Author

Listed:
  • Luis V. Valcárcel

    (Manuel de Lardizábal 13
    CCUN)

  • Edurne San José-Enériz

    (CCUN
    CIBERONC Centro de Investigación Biomédica en Red de Cáncer)

  • Raquel Ordoñez

    (CCUN
    CIBERONC Centro de Investigación Biomédica en Red de Cáncer)

  • Iñigo Apaolaza

    (Manuel de Lardizábal 13)

  • Danel Olaverri-Mendizabal

    (Manuel de Lardizábal 13)

  • Naroa Barrena

    (Manuel de Lardizábal 13)

  • Ana Valcárcel

    (CCUN)

  • Leire Garate

    (CCUN
    CIBERONC Centro de Investigación Biomédica en Red de Cáncer)

  • Jesús San Miguel

    (CCUN
    CIBERONC Centro de Investigación Biomédica en Red de Cáncer
    Universidad de Navarra)

  • Antonio Pineda-Lucena

    (CCUN
    CIBERONC Centro de Investigación Biomédica en Red de Cáncer)

  • Xabier Agirre

    (CCUN
    CIBERONC Centro de Investigación Biomédica en Red de Cáncer)

  • Felipe Prósper

    (CCUN
    CIBERONC Centro de Investigación Biomédica en Red de Cáncer
    Universidad de Navarra)

  • Francisco J. Planes

    (Manuel de Lardizábal 13
    University of Navarra
    Campus Universitario)

Abstract

The development of computational tools for the systematic prediction of metabolic vulnerabilities of cancer cells constitutes a central question in systems biology. Here, we present gmctool, a freely accessible online tool that allows us to accomplish this task in a simple, efficient and intuitive environment. gmctool exploits the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to synthetic lethality based on genome-scale metabolic networks, including a unique database of synthetic lethals computed from Human1, the most recent metabolic reconstruction of human cells. gmctool introduces qualitative and quantitative improvements over our previously developed algorithms to predict, visualize and analyze metabolic vulnerabilities in cancer, demonstrating a superior performance than competing algorithms. A detailed illustration of gmctool is presented for multiple myeloma (MM), an incurable hematological malignancy. We provide in vitro experimental evidence for the essentiality of CTPS1 (CTPS synthase) and UAP1 (UDP-N-Acetylglucosamine Pyrophosphorylase 1) in specific MM patient subgroups.

Suggested Citation

  • Luis V. Valcárcel & Edurne San José-Enériz & Raquel Ordoñez & Iñigo Apaolaza & Danel Olaverri-Mendizabal & Naroa Barrena & Ana Valcárcel & Leire Garate & Jesús San Miguel & Antonio Pineda-Lucena & Xab, 2024. "An automated network-based tool to search for metabolic vulnerabilities in cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52725-4
    DOI: 10.1038/s41467-024-52725-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52725-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52725-4?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. Nicola A. Thompson & Marco Ranzani & Louise Weyden & Vivek Iyer & Victoria Offord & Alastair Droop & Fiona Behan & Emanuel Gonçalves & Anneliese Speak & Francesco Iorio & James Hewinson & Victoria Har, 2021. "Combinatorial CRISPR screen identifies fitness effects of gene paralogues," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    2. Jung-Lin Wu & Ming-Feng Chiang & Pan-Hung Hsu & Dong-Yen Tsai & Kuo-Hsuan Hung & Ying-Hsiu Wang & Takashi Angata & Kuo-I Lin, 2017. "O-GlcNAcylation is required for B cell homeostasis and antibody responses," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    3. Xabier Agirre & Cem Meydan & Yanwen Jiang & Leire Garate & Ashley S. Doane & Zhuoning Li & Akanksha Verma & Bruno Paiva & José I. Martín-Subero & Olivier Elemento & Christopher E. Mason & Felipe Prosp, 2019. "Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    4. Florian L. Muller & Simona Colla & Elisa Aquilanti & Veronica E. Manzo & Giannicola Genovese & Jaclyn Lee & Daniel Eisenson & Rujuta Narurkar & Pingna Deng & Luigi Nezi & Michelle A. Lee & Baoli Hu & , 2012. "Passenger deletions generate therapeutic vulnerabilities in cancer," Nature, Nature, vol. 488(7411), pages 337-342, August.
    5. Shuting Li & Chia-Wen Lu & Elia C. Diem & Wang Li & Melanie Guderian & Marc Lindenberg & Friederike Kruse & Manuela Buettner & Stefan Floess & Markus R. Winny & Robert Geffers & Hans-Hermann Richnow &, 2022. "Acetyl-CoA-Carboxylase 1-mediated de novo fatty acid synthesis sustains Lgr5+ intestinal stem cell function," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Luis Tobalina & Jon Pey & Alberto Rezola & Francisco J Planes, 2016. "Assessment of FBA Based Gene Essentiality Analysis in Cancer with a Fast Context-Specific Network Reconstruction Method," PLOS ONE, Public Library of Science, vol. 11(5), pages 1-17, May.
    7. Iñigo Apaolaza & Edurne San José-Eneriz & Luis Tobalina & Estíbaliz Miranda & Leire Garate & Xabier Agirre & Felipe Prósper & Francisco J. Planes, 2017. "An in-silico approach to predict and exploit synthetic lethality in cancer metabolism," Nature Communications, Nature, vol. 8(1), pages 1-9, 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. Sumana Srivatsa & Hesam Montazeri & Gaia Bianco & Mairene Coto-Llerena & Mattia Marinucci & Charlotte K. Y. Ng & Salvatore Piscuoglio & Niko Beerenwinkel, 2022. "Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Anne Richelle & Austin W T Chiang & Chih-Chung Kuo & Nathan E Lewis, 2019. "Increasing consensus of context-specific metabolic models by integrating data-inferred cell functions," PLOS Computational Biology, Public Library of Science, vol. 15(4), pages 1-19, April.
    3. Ruitong Li & Olaf Klingbeil & Davide Monducci & Michael J. Young & Diego J. Rodriguez & Zaid Bayyat & Joshua M. Dempster & Devishi Kesar & Xiaoping Yang & Mahdi Zamanighomi & Christopher R. Vakoc & Ta, 2022. "Comparative optimization of combinatorial CRISPR screens," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    4. Tanaz Sharifnia & Mathias J. Wawer & Amy Goodale & Yenarae Lee & Mariya Kazachkova & Joshua M. Dempster & Sandrine Muller & Joan Levy & Daniel M. Freed & Josh Sommer & Jérémie Kalfon & Francisca Vazqu, 2023. "Mapping the landscape of genetic dependencies in chordoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Nazanin Esmaeili Anvar & Chenchu Lin & Xingdi Ma & Lori L. Wilson & Ryan Steger & Annabel K. Sangree & Medina Colic & Sidney H. Wang & John G. Doench & Traver Hart, 2024. "Efficient gene knockout and genetic interaction screening using the in4mer CRISPR/Cas12a multiplex knockout platform," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Jian Ma & Lei Li & Bohan Ma & Tianjie Liu & Zixi Wang & Qi Ye & Yunhua Peng & Bin Wang & Yule Chen & Shan Xu & Ke Wang & Fabin Dang & Xinyang Wang & Zixuan Zeng & Yanlin Jian & Zhihua Ren & Yizeng Fan, 2024. "MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Li Wang & Yun Xiao & Yanyan Ping & Jing Li & Hongying Zhao & Feng Li & Jing Hu & Hongyi Zhang & Yulan Deng & Jiawei Tian & Xia Li, 2014. "Integrating Multi-Omics for Uncovering the Architecture of Cross-Talking Pathways in Breast Cancer," PLOS ONE, Public Library of Science, vol. 9(8), pages 1-10, August.

    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:15:y:2024:i:1:d:10.1038_s41467-024-52725-4. 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.