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Accurate prediction of protein function using statistics-informed graph networks

Author

Listed:
  • Yaan J. Jang

    (University of Oxford
    AmoAi Technologies)

  • Qi-Qi Qin

    (AmoAi Technologies
    University of Shanghai for Science and Technology)

  • Si-Yu Huang

    (AmoAi Technologies
    University of Oxford
    Beijing Normal University)

  • Arun T. John Peter

    (ETH Zürich)

  • Xue-Ming Ding

    (University of Shanghai for Science and Technology)

  • Benoît Kornmann

    (University of Oxford)

Abstract

Understanding protein function is pivotal in comprehending the intricate mechanisms that underlie many crucial biological activities, with far-reaching implications in the fields of medicine, biotechnology, and drug development. However, more than 200 million proteins remain uncharacterized, and computational efforts heavily rely on protein structural information to predict annotations of varying quality. Here, we present a method that utilizes statistics-informed graph networks to predict protein functions solely from its sequence. Our method inherently characterizes evolutionary signatures, allowing for a quantitative assessment of the significance of residues that carry out specific functions. PhiGnet not only demonstrates superior performance compared to alternative approaches but also narrows the sequence-function gap, even in the absence of structural information. Our findings indicate that applying deep learning to evolutionary data can highlight functional sites at the residue level, providing valuable support for interpreting both existing properties and new functionalities of proteins in research and biomedicine.

Suggested Citation

  • Yaan J. Jang & Qi-Qi Qin & Si-Yu Huang & Arun T. John Peter & Xue-Ming Ding & Benoît Kornmann, 2024. "Accurate prediction of protein function using statistics-informed graph networks," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50955-0
    DOI: 10.1038/s41467-024-50955-0
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    References listed on IDEAS

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    1. Jonathan Frazer & Pascal Notin & Mafalda Dias & Aidan Gomez & Joseph K. Min & Kelly Brock & Yarin Gal & Debora S. Marks, 2021. "Disease variant prediction with deep generative models of evolutionary data," Nature, Nature, vol. 599(7883), pages 91-95, November.
    2. Lukas F. Milles & Eduard M. Unterauer & Thomas Nicolaus & Hermann E. Gaub, 2018. "Calcium stabilizes the strongest protein fold," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    3. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    4. Vladimir Gligorijević & P. Douglas Renfrew & Tomasz Kosciolek & Julia Koehler Leman & Daniel Berenberg & Tommi Vatanen & Chris Chandler & Bryn C. Taylor & Ian M. Fisk & Hera Vlamakis & Ramnik J. Xavie, 2021. "Structure-based protein function prediction using graph convolutional networks," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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