IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46901-9.html
   My bibliography  Save this article

Precise prediction of phase-separation key residues by machine learning

Author

Listed:
  • Jun Sun

    (Sichuan University
    Sichuan University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Jiale Qu

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Cai Zhao

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Xinyao Zhang

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Xinyu Liu

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Jia Wang

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University
    Guangzhou Medical University)

  • Chao Wei

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Xinyi Liu

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Mulan Wang

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Pengguihang Zeng

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Xiuxiao Tang

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Xiaoru Ling

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Li Qing

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Shaoshuai Jiang

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Jiahao Chen

    (Sun Yat-sen University
    Sun Yat-sen University
    Sun Yat-sen University)

  • Tara S. R. Chen

    (Sun Yat-Sen University)

  • Yalan Kuang

    (Sichuan University
    Sichuan University)

  • Jinhang Gao

    (Sichuan University
    Sichuan University)

  • Xiaoxi Zeng

    (Sichuan University
    Sichuan University)

  • Dongfeng Huang

    (Sun Yat-Sen University)

  • Yong Yuan

    (Sichuan University
    Sichuan University)

  • Lili Fan

    (School of Traditional Chinese Medicine, Jinan University)

  • Haopeng Yu

    (Sichuan University
    Sichuan University)

  • Junjun Ding

    (Sichuan University
    Sichuan University
    Sun Yat-sen University
    Sun Yat-sen University)

Abstract

Understanding intracellular phase separation is crucial for deciphering transcriptional control, cell fate transitions, and disease mechanisms. However, the key residues, which impact phase separation the most for protein phase separation function have remained elusive. We develop PSPHunter, which can precisely predict these key residues based on machine learning scheme. In vivo and in vitro validations demonstrate that truncating just 6 key residues in GATA3 disrupts phase separation, enhancing tumor cell migration and inhibiting growth. Glycine and its motifs are enriched in spacer and key residues, as revealed by our comprehensive analysis. PSPHunter identifies nearly 80% of disease-associated phase-separating proteins, with frequent mutated pathological residues like glycine and proline often residing in these key residues. PSPHunter thus emerges as a crucial tool to uncover key residues, facilitating insights into phase separation mechanisms governing transcriptional control, cell fate transitions, and disease development.

Suggested Citation

  • Jun Sun & Jiale Qu & Cai Zhao & Xinyao Zhang & Xinyu Liu & Jia Wang & Chao Wei & Xinyi Liu & Mulan Wang & Pengguihang Zeng & Xiuxiao Tang & Xiaoru Ling & Li Qing & Shaoshuai Jiang & Jiahao Chen & Tara, 2024. "Precise prediction of phase-separation key residues by machine learning," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46901-9
    DOI: 10.1038/s41467-024-46901-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46901-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-46901-9?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. Charles H. Li & Eliot L. Coffey & Alessandra Dall’Agnese & Nancy M. Hannett & Xin Tang & Jonathan E. Henninger & Jesse M. Platt & Ozgur Oksuz & Alicia V. Zamudio & Lena K. Afeyan & Jurian Schuijers & , 2020. "MeCP2 links heterochromatin condensates and neurodevelopmental disease," Nature, Nature, vol. 586(7829), pages 440-444, October.
    2. Xiaoxia Yang & Jia Wang & Jun Sun & Rong Liu, 2015. "SNBRFinder: A Sequence-Based Hybrid Algorithm for Enhanced Prediction of Nucleic Acid-Binding Residues," PLOS ONE, Public Library of Science, vol. 10(7), pages 1-23, July.
    3. Fides Zenk & Yinxiu Zhan & Pavel Kos & Eva Löser & Nazerke Atinbayeva & Melanie Schächtle & Guido Tiana & Luca Giorgetti & Nicola Iovino, 2021. "HP1 drives de novo 3D genome reorganization in early Drosophila embryos," Nature, Nature, vol. 593(7858), pages 289-293, May.
    4. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    5. Matthew R. King & Sabine Petry, 2020. "Phase separation of TPX2 enhances and spatially coordinates microtubule nucleation," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    6. Pilong Li & Sudeep Banjade & Hui-Chun Cheng & Soyeon Kim & Baoyu Chen & Liang Guo & Marc Llaguno & Javoris V. Hollingsworth & David S. King & Salman F. Banani & Paul S. Russo & Qiu-Xing Jiang & B. Tra, 2012. "Phase transitions in the assembly of multivalent signalling proteins," Nature, Nature, vol. 483(7389), pages 336-340, March.
    7. W. Michael Babinchak & Benjamin K. Dumm & Sarah Venus & Solomiia Boyko & Andrea A. Putnam & Eckhard Jankowsky & Witold K. Surewicz, 2020. "Small molecules as potent biphasic modulators of protein liquid-liquid phase separation," Nature Communications, Nature, vol. 11(1), pages 1-15, 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. Beatrice Ramm & Dominik Schumacher & Andrea Harms & Tamara Heermann & Philipp Klos & Franziska Müller & Petra Schwille & Lotte Søgaard-Andersen, 2023. "Biomolecular condensate drives polymerization and bundling of the bacterial tubulin FtsZ to regulate cell division," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    2. Dafne Ibarra-Morales & Michael Rauer & Piergiuseppe Quarato & Leily Rabbani & Fides Zenk & Mariana Schulte-Sasse & Francesco Cardamone & Alejandro Gomez-Auli & Germano Cecere & Nicola Iovino, 2021. "Histone variant H2A.Z regulates zygotic genome activation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Maruša Ramšak & Dominique A. Ramirez & Loren E. Hough & Michael R. Shirts & Sara Vidmar & Kristina Eleršič Filipič & Gregor Anderluh & Roman Jerala, 2023. "Programmable de novo designed coiled coil-mediated phase separation in mammalian cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Furqan Dar & Samuel R. Cohen & Diana M. Mitrea & Aaron H. Phillips & Gergely Nagy & Wellington C. Leite & Christopher B. Stanley & Jeong-Mo Choi & Richard W. Kriwacki & Rohit V. Pappu, 2024. "Biomolecular condensates form spatially inhomogeneous network fluids," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    5. Xiangwei Li & Thomas Delerue & Ben Schöttker & Bernd Holleczek & Eva Grill & Annette Peters & Melanie Waldenberger & Barbara Thorand & Hermann Brenner, 2022. "Derivation and validation of an epigenetic frailty risk score in population-based cohorts of older adults," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    6. Shuangcheng Alivia Wu & Chenchen Shen & Xiaoqiong Wei & Xiawei Zhang & Siwen Wang & Xinxin Chen & Mauricio Torres & You Lu & Liangguang Leo Lin & Huilun Helen Wang & Allen H. Hunter & Deyu Fang & Shen, 2023. "The mechanisms to dispose of misfolded proteins in the endoplasmic reticulum of adipocytes," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Yasuhiko Haga & Yoshitaka Sakamoto & Keiko Kajiya & Hitomi Kawai & Miho Oka & Noriko Motoi & Masayuki Shirasawa & Masaya Yotsukura & Shun-Ichi Watanabe & Miyuki Arai & Junko Zenkoh & Kouya Shiraishi &, 2023. "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Jialiang S. Wang & Tushar Kamath & Courtney M. Mazur & Fatemeh Mirzamohammadi & Daniel Rotter & Hironori Hojo & Christian D. Castro & Nicha Tokavanich & Rushi Patel & Nicolas Govea & Tetsuya Enishi & , 2021. "Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    9. Zheng Shen & Daxiao Sun & Adriana Savastano & Sára Joana Varga & Maria-Sol Cima-Omori & Stefan Becker & Alf Honigmann & Markus Zweckstetter, 2023. "Multivalent Tau/PSD-95 interactions arrest in vitro condensates and clusters mimicking the postsynaptic density," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    10. Ryan J. Geusz & Allen Wang & Dieter K. Lam & Nicholas K. Vinckier & Konstantinos-Dionysios Alysandratos & David A. Roberts & Jinzhao Wang & Samy Kefalopoulou & Araceli Ramirez & Yunjiang Qiu & Joshua , 2021. "Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    11. Andreas Herchenröther & Stefanie Gossen & Tobias Friedrich & Alexander Reim & Nadine Daus & Felix Diegmüller & Jörg Leers & Hakimeh Moghaddas Sani & Sarah Gerstner & Leah Schwarz & Inga Stellmacher & , 2023. "The H2A.Z and NuRD associated protein HMG20A controls early head and heart developmental transcription programs," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    12. Aftab Nadeem & Athar Alam & Eric Toh & Si Lhyam Myint & Zia ur Rehman & Tao Liu & Marta Bally & Anna Arnqvist & Hui Wang & Jun Zhu & Karina Persson & Bernt Eric Uhlin & Sun Nyunt Wai, 2021. "Phosphatidic acid-mediated binding and mammalian cell internalization of the Vibrio cholerae cytotoxin MakA," PLOS Pathogens, Public Library of Science, vol. 17(3), pages 1-34, March.
    13. Hao A. Duong & Kenkichi Baba & Jason P. DeBruyne & Alec J. Davidson & Christopher Ehlen & Michael Powell & Gianluca Tosini, 2024. "Environmental circadian disruption re-writes liver circadian proteomes," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    14. Xuelong Yao & Zongyang Lu & Zhanying Feng & Lei Gao & Xin Zhou & Min Li & Suijuan Zhong & Qian Wu & Zhenbo Liu & Haofeng Zhang & Zeyuan Liu & Lizhi Yi & Tao Zhou & Xudong Zhao & Jun Zhang & Yong Wang , 2022. "Comparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    15. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    16. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    17. Li Guo & Cheng Hu & Yang Liu & Xiaoyu Chen & Deli Song & Runling Shen & Zhanzhen Liu & Xudong Jia & Qinfen Zhang & Yuanzhu Gao & Zhezhi Deng & Tao Zuo & Jun Hu & Wenbo Zhu & Jing Cai & Guangmei Yan & , 2023. "Directed natural evolution generates a next-generation oncolytic virus with a high potency and safety profile," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Mijeong Kim & Yu Jin Jang & Muyoung Lee & Qingqing Guo & Albert J. Son & Nikita A. Kakkad & Abigail B. Roland & Bum-Kyu Lee & Jonghwan Kim, 2024. "The transcriptional regulatory network modulating human trophoblast stem cells to extravillous trophoblast differentiation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    19. Alejandro Gomez Toledo & Eleni Bratanis & Erika Velásquez & Sounak Chowdhury & Berit Olofsson & James T. Sorrentino & Christofer Karlsson & Nathan E. Lewis & Jeffrey D. Esko & Mattias Collin & Oonagh , 2023. "Pathogen-driven degradation of endogenous and therapeutic antibodies during streptococcal infections," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    20. Cecilia Pessoa Rodrigues & Aindrila Chatterjee & Meike Wiese & Thomas Stehle & Witold Szymanski & Maria Shvedunova & Asifa Akhtar, 2021. "Histone H4 lysine 16 acetylation controls central carbon metabolism and diet-induced obesity in mice," Nature Communications, Nature, vol. 12(1), pages 1-21, 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:15:y:2024:i:1:d:10.1038_s41467-024-46901-9. 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.