IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43967-9.html
   My bibliography  Save this article

ACIDES: on-line monitoring of forward genetic screens for protein engineering

Author

Listed:
  • Takahiro Nemoto

    (Sorbonne Université, INSERM, CNRS
    Kyoto University, Yoshida Hon-machi
    Osaka University)

  • Tommaso Ocari

    (Sorbonne Université, INSERM, CNRS)

  • Arthur Planul

    (Sorbonne Université, INSERM, CNRS)

  • Muge Tekinsoy

    (Sorbonne Université, INSERM, CNRS)

  • Emilia A. Zin

    (Sorbonne Université, INSERM, CNRS)

  • Deniz Dalkara

    (Sorbonne Université, INSERM, CNRS)

  • Ulisse Ferrari

    (Sorbonne Université, INSERM, CNRS)

Abstract

Forward genetic screens of mutated variants are a versatile strategy for protein engineering and investigation, which has been successfully applied to various studies like directed evolution (DE) and deep mutational scanning (DMS). While next-generation sequencing can track millions of variants during the screening rounds, the vast and noisy nature of the sequencing data impedes the estimation of the performance of individual variants. Here, we propose ACIDES that combines statistical inference and in-silico simulations to improve performance estimation in the library selection process by attributing accurate statistical scores to individual variants. We tested ACIDES first on a random-peptide-insertion experiment and then on multiple public datasets from DE and DMS studies. ACIDES allows experimentalists to reliably estimate variant performance on the fly and can aid protein engineering and research pipelines in a range of applications, including gene therapy.

Suggested Citation

  • Takahiro Nemoto & Tommaso Ocari & Arthur Planul & Muge Tekinsoy & Emilia A. Zin & Deniz Dalkara & Ulisse Ferrari, 2023. "ACIDES: on-line monitoring of forward genetic screens for protein engineering," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43967-9
    DOI: 10.1038/s41467-023-43967-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43967-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43967-9?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. Liselot Dewachter & Aaron N. Brooks & Katherine Noon & Charlotte Cialek & Alia Clark-ElSayed & Thomas Schalck & Nandini Krishnamurthy & Wim Versées & Wim Vranken & Jan Michiels, 2023. "Deep mutational scanning of essential bacterial proteins can guide antibiotic development," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Liselot Dewachter & Aaron N. Brooks & Katherine Noon & Charlotte Cialek & Alia Clark-ElSayed & Thomas Schalck & Nandini Krishnamurthy & Wim Versées & Wim Vranken & Jan Michiels, 2023. "Author Correction: Deep mutational scanning of essential bacterial proteins can guide antibiotic development," Nature Communications, Nature, vol. 14(1), pages 1-1, December.
    3. Maximilian Puelma Touzel & Aleksandra M Walczak & Thierry Mora, 2020. "Inferring the immune response from repertoire sequencing," PLOS Computational Biology, Public Library of Science, vol. 16(4), pages 1-21, April.
    4. Júlia Domingo & Guillaume Diss & Ben Lehner, 2018. "Pairwise and higher-order genetic interactions during the evolution of a tRNA," Nature, Nature, vol. 558(7708), pages 117-121, June.
    5. Benedetta Bolognesi & Andre J. Faure & Mireia Seuma & Jörn M. Schmiedel & Gian Gaetano Tartaglia & Ben Lehner, 2019. "The mutational landscape of a prion-like domain," 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. Rachapun Rotrattanadumrong & Yohei Yokobayashi, 2022. "Experimental exploration of a ribozyme neutral network using evolutionary algorithm and deep learning," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Karol Buda & Charlotte M. Miton & Nobuhiko Tokuriki, 2023. "Pervasive epistasis exposes intramolecular networks in adaptive enzyme evolution," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Yeonwoo Park & Brian P. H. Metzger & Joseph W. Thornton, 2024. "The simplicity of protein sequence-function relationships," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Mireia Seuma & Ben Lehner & Benedetta Bolognesi, 2022. "An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Andreas Wagner, 2023. "Evolvability-enhancing mutations in the fitness landscapes of an RNA and a protein," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Ziyi Zhou & Liang Zhang & Yuanxi Yu & Banghao Wu & Mingchen Li & Liang Hong & Pan Tan, 2024. "Enhancing efficiency of protein language models with minimal wet-lab data through few-shot learning," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Rosa Antón & Miguel Á. Treviño & David Pantoja-Uceda & Sara Félix & María Babu & Eurico J. Cabrita & Markus Zweckstetter & Philip Tinnefeld & Andrés M. Vera & Javier Oroz, 2024. "Alternative low-populated conformations prompt phase transitions in polyalanine repeat expansions," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Jaime Carrasco & Rosa Antón & Alejandro Valbuena & David Pantoja-Uceda & Mayur Mukhi & Rubén Hervás & Douglas V. Laurents & María Gasset & Javier Oroz, 2023. "Metamorphism in TDP-43 prion-like domain determines chaperone recognition," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Solip Park & Fran Supek & Ben Lehner, 2021. "Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers," Nature Communications, Nature, vol. 12(1), pages 1-10, 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_s41467-023-43967-9. 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.