PARADIGM-SHIFT predicts the function of mutations in multiple cancers using pathway impact analysis

被引:75
|
作者
Ng, Sam [1 ,2 ]
Collisson, Eric A. [3 ]
Sokolov, Artem [1 ,2 ]
Goldstein, Theodore [1 ,2 ]
Gonzalez-Perez, Abel [4 ]
Lopez-Bigas, Nuria [5 ,6 ]
Benz, Christopher [7 ]
Haussler, David [1 ,2 ,8 ]
Stuart, Joshua M. [1 ,2 ]
机构
[1] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA
[2] Univ Calif Santa Cruz, CBSE, Santa Cruz, CA 95064 USA
[3] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA
[4] Parc Recerca Biomed Barcelona, E-08003 Barcelona, Spain
[5] Univ Pompeu Fabra, E-08002 Barcelona, Spain
[6] ICREA, E-08010 Barcelona, Spain
[7] Univ Calif Santa Cruz, Buck Inst Aging, Unit Christopher Benz, Canc Therapeut Program Novato 94945, Santa Cruz, CA 95064 USA
[8] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA
基金
美国国家科学基金会;
关键词
D O I
10.1093/bioinformatics/bts402
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Motivation: A current challenge in understanding cancer processes is to pinpoint which mutations influence the onset and progression of disease. Toward this goal, we describe a method called PARADIGM-SHIFT that can predict whether a mutational event is neutral, gain- or loss-of-function in a tumor sample. The method uses a belief-propagation algorithm to infer gene activity from gene expression and copy number data in the context of a set of pathway interactions. Results: The method was found to be both sensitive and specific on a set of positive and negative controls for multiple cancers for which pathway information was available. Application to the Cancer Genome Atlas glioblastoma, ovarian and lung squamous cancer datasets revealed several novel mutations with predicted high impact including several genes mutated at low frequency suggesting the approach will be complementary to current approaches that rely on the prevalence of events to reach statistical significance.
引用
收藏
页码:I640 / I646
页数:7
相关论文
共 50 条
  • [1] PARADIGM-SHIFT: Predicts the functional impact of 'driver modules' in multiple cancers using pathway impact analysis
    Ng, Sam
    Benz, Christopher
    Haussler, David
    Stuart, Joshua M.
    CANCER RESEARCH, 2015, 75 (22)
  • [2] THERAPIST-PATIENT RELATIONSHIP - CONCEPTUAL ANALYSIS AND A PROPOSAL FOR A PARADIGM-SHIFT
    MAHRER, A
    PSYCHOTHERAPY-THEORY RESEARCH AND PRACTICE, 1978, 15 (03): : 201 - 215
  • [3] Impact of COVID-19 on Education & the Analysis of the Paradigm-shift of Offline Learning to E-Learning
    Bansal, Kapil
    BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS, 2020, 13 (10): : 207 - 210
  • [4] Patient-specific pathway analysis using PARADIGM identifies key activities in multiple cancers
    Benz, Stephen C.
    Vaske, Charles
    Ng, Sam
    Sanborn, John Zachary
    Zhu, Jing
    Haussler, David
    Stuart, Joshua
    CANCER RESEARCH, 2011, 71
  • [5] The 'paradigm-shift' in advanced ovarian cancer: outcomes of extensive cytoreductive surgery. A single center retrospective analysis
    Bianchi, Tommaso
    Testa, Filippo
    Bazzurini, Luca
    Grassi, Tommaso
    Corti, Jasmine
    Martino, Giampaolo Di
    Trezzi, Gaetano
    Marino, Giuseppe
    Ponti, Elena De
    Fruscio, Robert
    Landoni, Fabio
    INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2024, 34 (SUPPL_1) : A351 - A352
  • [6] Modeling the impact of mutations in ubiquitin pathway genes across human cancers
    Osmanbeyoglu, Hatice U.
    Leslie, Christina
    CANCER RESEARCH, 2017, 77
  • [7] mTOR pathway gene mutations predict response to immune checkpoint inhibitors in multiple cancers
    Lei Cheng
    Yanan Wang
    Lixin Qiu
    Yuanyuan Chang
    Haijiao Lu
    Chenchen Liu
    Bo Zhang
    Yan Zhou
    Hao Bai
    Liwen Xiong
    Hua Zhong
    Wei Nie
    Baohui Han
    Journal of Translational Medicine, 20
  • [8] mTOR pathway gene mutations predict response to immune checkpoint inhibitors in multiple cancers
    Cheng, Lei
    Wang, Yanan
    Qiu, Lixin
    Chang, Yuanyuan
    Lu, Haijiao
    Liu, Chenchen
    Zhang, Bo
    Zhou, Yan
    Bai, Hao
    Xiong, Liwen
    Zhong, Hua
    Nie, Wei
    Han, Baohui
    JOURNAL OF TRANSLATIONAL MEDICINE, 2022, 20 (01)
  • [9] Patient-specific pathway analysis using DIGMA identifies key activities in multiple cancers
    Benz, Stephen
    Vaske, Charles
    Sanborn, J. Zachary
    Stuart, Joshua
    Haussler, David
    CANCER RESEARCH, 2010, 70
  • [10] Patient-specific pathway analysis using DIGMA identifies key activities in multiple cancers
    Benz, Stephen
    Vaske, Charles
    Sanborn, J. Zachary
    Stuart, Joshua
    Haussler, David
    CANCER RESEARCH, 2010, 70