Department of Biology, University of Padova, Via U.Bassi 58B, 35121 Padova, Italy.
Department of Statistical Sciences 'Paolo Fortunati', University of Bologna, via delle Belle Arti 41, 40126 Bologna, Italy.
Nucleic Acids Res. 2019 Aug 22;47(14):e80. doi: 10.1093/nar/gkz324.
Survival analyses of gene expression data has been a useful and widely used approach in clinical applications. But, in complex diseases, such as cancer, the identification of survival-associated cell processes - rather than single genes - provides more informative results because the efficacy of survival prediction increases when multiple prognostic features are combined to enlarge the possibility of having druggable targets. Moreover, genome-wide screening in molecular medicine has rapidly grown, providing not only gene expression but also multi-omic measurements such as DNA mutations, methylation, expression, and copy number data. In cancer, virtually all these aberrations can contribute in synergy to pathological processes, and their measurements can improve a patient's outcome and help in diagnosis and treatment decisions. Here, we present MOSClip, an R package implementing a new topological pathway analysis tool able to integrate multi-omic data and look for survival-associated gene modules. MOSClip tests the survival association of dimensionality-reduced multi-omic data using multivariate models, providing graphical devices for management, browsing and interpretation of results. Using simulated data we evaluated MOSClip performance in terms of false positives and false negatives in different settings, while the TCGA ovarian cancer dataset is used as a case study to highlight MOSClip's potential.
生存分析是一种在临床应用中非常有用且广泛使用的基因表达数据分析方法。但是,在复杂疾病(如癌症)中,识别与生存相关的细胞过程(而不是单个基因)可以提供更具信息量的结果,因为当多个预后特征结合在一起以增加获得可药物治疗靶点的可能性时,生存预测的效果会提高。此外,分子医学中的全基因组筛选迅速发展,不仅提供了基因表达数据,还提供了多组学测量数据,如 DNA 突变、甲基化、表达和拷贝数数据。在癌症中,几乎所有这些异常都可以协同作用于病理过程,它们的测量结果可以改善患者的预后,并有助于诊断和治疗决策。在这里,我们介绍了 MOSClip,这是一个 R 包,实现了一种新的拓扑通路分析工具,能够整合多组学数据并寻找与生存相关的基因模块。MOSClip 使用多变量模型来测试降维多组学数据的生存相关性,提供了用于管理、浏览和解释结果的图形设备。我们使用模拟数据评估了 MOSClip 在不同环境下的假阳性和假阴性性能,同时使用 TCGA 卵巢癌数据集作为案例研究来突出 MOSClip 的潜力。