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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
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    References listed on IDEAS

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    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. 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.
    3. 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.
    4. 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.
    5. 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.
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