论文标题
用于混合图形模型学习的可伸缩生气死亡MCMC算法,并应用于基因组数据集成
The scalable Birth-Death MCMC Algorithm for Mixed Graphical Model Learning with Application to Genomic Data Integration
论文作者
论文摘要
生物学研究的最新进展使高通量技术的出现具有许多应用,这些应用允许研究以空前的深度和规模研究生物学机制。现在,大量基因组数据通过癌症基因组图集(TCGA)分布,其中特定类型的生物学信息有关特定类型的组织或细胞。在癌症研究中,挑战现在是对高维多摩尼数据进行的综合分析,其目标是更好地了解与癌症结局相关的基因组过程,例如阐明区分特定癌症亚组(癌症亚型)或发现与不同癌症类型重叠的基因网络的基因网络(PAN-CASCER研究)。在本文中,我们提出了一种新型的混合图形模型方法,用于分析不同类型(连续,离散和计数)的多摩变数据,并通过扩展最初提出的\ citet {stephens2000bayesian}和后来由\ citeian Ians开发的\ citet {Mohammadi2015的出生死亡MCMC(BDMCMC)算法来执行模型选择。我们使用模拟将方法的性能与LASSO方法和标准BDMCMC方法进行了比较,并发现我们的方法在计算效率和模型选择结果的准确性方面都很出色。最后,对TCGA乳腺癌数据的应用表明,在不同水平(突变和表达数据)上整合基因组信息会导致乳腺癌的更好亚型。
Recent advances in biological research have seen the emergence of high-throughput technologies with numerous applications that allow the study of biological mechanisms at an unprecedented depth and scale. A large amount of genomic data is now distributed through consortia like The Cancer Genome Atlas (TCGA), where specific types of biological information on specific type of tissue or cell are available. In cancer research, the challenge is now to perform integrative analyses of high-dimensional multi-omic data with the goal to better understand genomic processes that correlate with cancer outcomes, e.g. elucidate gene networks that discriminate a specific cancer subgroups (cancer sub-typing) or discovering gene networks that overlap across different cancer types (pan-cancer studies). In this paper, we propose a novel mixed graphical model approach to analyze multi-omic data of different types (continuous, discrete and count) and perform model selection by extending the Birth-Death MCMC (BDMCMC) algorithm initially proposed by \citet{stephens2000bayesian} and later developed by \cite{mohammadi2015bayesian}. We compare the performance of our method to the LASSO method and the standard BDMCMC method using simulations and find that our method is superior in terms of both computational efficiency and the accuracy of the model selection results. Finally, an application to the TCGA breast cancer data shows that integrating genomic information at different levels (mutation and expression data) leads to better subtyping of breast cancers.