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A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers

Author

Listed:
  • David Wang

    (University of Pennsylvania
    Perelman School of Medicine, University of Pennsylvania)

  • Mathieu Quesnel-Vallieres

    (University of Pennsylvania
    Perelman School of Medicine, University of Pennsylvania)

  • San Jewell

    (University of Pennsylvania)

  • Moein Elzubeir

    (University of Pennsylvania)

  • Kristen Lynch

    (University of Pennsylvania
    Perelman School of Medicine, University of Pennsylvania)

  • Andrei Thomas-Tikhonenko

    (Perelman School of Medicine, University of Pennsylvania
    Children’s Hospital of Philadelphia)

  • Yoseph Barash

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

Identification of cancer sub-types is a pivotal step for developing personalized treatment. Specifically, sub-typing based on changes in RNA splicing has been motivated by several recent studies. We thus develop CHESSBOARD, an unsupervised algorithm tailored for RNA splicing data that captures “tiles” in the data, defined by a subset of unique splicing changes in a subset of patients. CHESSBOARD allows for a flexible number of tiles, accounts for uncertainty of splicing quantification, and is able to model missing values as additional signals. We first apply CHESSBOARD to synthetic data to assess its domain specific modeling advantages, followed by analysis of several leukemia datasets. We show detected tiles are reproducible in independent studies, investigate their possible regulatory drivers and probe their relation to known AML mutations. Finally, we demonstrate the potential clinical utility of CHESSBOARD by supplementing mutation based diagnostic assays with discovered splicing profiles to improve drug response correlation.

Suggested Citation

  • David Wang & Mathieu Quesnel-Vallieres & San Jewell & Moein Elzubeir & Kristen Lynch & Andrei Thomas-Tikhonenko & Yoseph Barash, 2023. "A Bayesian model for unsupervised detection of RNA splicing based subtypes in cancers," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-022-35369-0
    DOI: 10.1038/s41467-022-35369-0
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    1. Jeffrey W. Tyner & Cristina E. Tognon & Daniel Bottomly & Beth Wilmot & Stephen E. Kurtz & Samantha L. Savage & Nicola Long & Anna Reister Schultz & Elie Traer & Melissa Abel & Anupriya Agarwal & Auro, 2018. "Functional genomic landscape of acute myeloid leukaemia," Nature, Nature, vol. 562(7728), pages 526-531, October.
    2. Eric L. Nostrand & Peter Freese & Gabriel A. Pratt & Xiaofeng Wang & Xintao Wei & Rui Xiao & Steven M. Blue & Jia-Yu Chen & Neal A. L. Cody & Daniel Dominguez & Sara Olson & Balaji Sundararaman & Liju, 2020. "A large-scale binding and functional map of human RNA-binding proteins," Nature, Nature, vol. 583(7818), pages 711-719, July.
    3. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Correction: Corrigendum: Signatures of mutational processes in human cancer," Nature, Nature, vol. 502(7470), pages 258-258, October.
    4. Ludmil B. Alexandrov & Serena Nik-Zainal & David C. Wedge & Samuel A. J. R. Aparicio & Sam Behjati & Andrew V. Biankin & Graham R. Bignell & Niccolò Bolli & Ake Borg & Anne-Lise Børresen-Dale & Sandri, 2013. "Signatures of mutational processes in human cancer," Nature, Nature, vol. 500(7463), pages 415-421, August.
    5. Su-In Lee & Safiye Celik & Benjamin A. Logsdon & Scott M. Lundberg & Timothy J. Martins & Vivian G. Oehler & Elihu H. Estey & Chris P. Miller & Sylvia Chien & Jin Dai & Akanksha Saxena & C. Anthony Bl, 2018. "A machine learning approach to integrate big data for precision medicine in acute myeloid leukemia," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    6. Xiaotu Ma & Yu Liu & Yanling Liu & Ludmil B. Alexandrov & Michael N. Edmonson & Charles Gawad & Xin Zhou & Yongjin Li & Michael C. Rusch & John Easton & Robert Huether & Veronica Gonzalez-Pena & Mark , 2018. "Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours," Nature, Nature, vol. 555(7696), pages 371-376, March.
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