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贝叶斯分层变稀疏回归模型及其在癌症蛋白质基因组学中的应用

Bayesian Hierarchical Varying-sparsity Regression Models with Application to Cancer Proteogenomics.

作者信息

Ni Yang, Stingo Francesco C, Ha Min Jin, Akbani Rehan, Baladandayuthapani Veerabhadran

机构信息

Department of Statistics and Data Sciences, The University of Texas at Austin.

Department of Statistics, Computer Science, Applications "G. Parenti", The University of Florence.

出版信息

J Am Stat Assoc. 2019;114(525):48-60. doi: 10.1080/01621459.2018.1434529. Epub 2018 Aug 15.

Abstract

Identifying patient-specific prognostic biomarkers is of critical importance in developing personalized treatment for clinically and molecularly heterogeneous diseases such as cancer. In this article, we propose a novel regression framework, (BEHAVIOR) models to select clinically relevant disease markers by integrating proteogenomic (proteomic+genomic) and clinical data. Our methods allow flexible modeling of protein-gene relationships as well as induces sparsity in both protein-gene and protein-survival relationships, to select ge-nomically driven prognostic protein markers at the patient-level. Simulation studies demonstrate the superior performance of BEHAVIOR against competing method in terms of both protein marker selection and survival prediction. We apply BEHAV-IOR to The Cancer Genome Atlas (TCGA) proteogenomic pan-cancer data and find several interesting prognostic proteins and pathways that are shared across multiple cancers and some that exclusively pertain to specific cancers.

摘要

识别患者特异性的预后生物标志物对于开发针对癌症等临床和分子异质性疾病的个性化治疗至关重要。在本文中,我们提出了一种新颖的回归框架,即(BEHAVIOR)模型,通过整合蛋白质基因组学(蛋白质组学+基因组学)和临床数据来选择临床相关的疾病标志物。我们的方法允许对蛋白质-基因关系进行灵活建模,并在蛋白质-基因和蛋白质-生存关系中引入稀疏性,以在患者水平上选择基因组驱动的预后蛋白质标志物。模拟研究表明,BEHAVIOR在蛋白质标志物选择和生存预测方面均优于竞争方法。我们将BEHAVIOR应用于癌症基因组图谱(TCGA)蛋白质基因组泛癌数据,发现了几种有趣的预后蛋白质和途径,这些蛋白质和途径在多种癌症中共享,还有一些专门与特定癌症相关。

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