Manolakos Alexandros, Ochoa Idoia, Venkat Kartik, Goldsmith Andrea J, Gevaert Olivier
BMC Genomics. 2014;15 Suppl 10(Suppl 10):S8. doi: 10.1186/1471-2164-15-S10-S8. Epub 2014 Dec 12.
Identification of genomic patterns in tumors is an important problem, which would enable the community to understand and extend effective therapies across the current tissue-based tumor boundaries. With this in mind, in this work we develop a robust and fast algorithm to discover cancer driver genes using an unsupervised clustering of similarly expressed genes across cancer patients. Specifically, we introduce CaMoDi, a new method for module discovery which demonstrates superior performance across a number of computational and statistical metrics.
The proposed algorithm CaMoDi demonstrates effective statistical performance compared to the state of the art, and is algorithmically simple and scalable - which makes it suitable for tissue-independent genomic characterization of individual tumors as well as groups of tumors. We perform an extensive comparative study between CaMoDi and two previously developed methods (CONEXIC and AMARETTO), across 11 individual tumors and 8 combinations of tumors from The Cancer Genome Atlas. We demonstrate that CaMoDi is able to discover modules with better average consistency and homogeneity, with similar or better adjusted R2 performance compared to CONEXIC and AMARETTO.
We present a novel method for Cancer Module Discovery, CaMoDi, and demonstrate through extensive simulations on the TCGA Pan-Cancer dataset that it achieves comparable or better performance than that of CONEXIC and AMARETTO, while achieving an order-of-magnitude improvement in computational run time compared to the other methods.
识别肿瘤中的基因组模式是一个重要问题,这将使科学界能够跨越当前基于组织的肿瘤界限来理解和扩展有效的治疗方法。考虑到这一点,在这项工作中,我们开发了一种强大且快速的算法,通过对癌症患者中相似表达基因进行无监督聚类来发现癌症驱动基因。具体而言,我们引入了CaMoDi,这是一种用于模块发现的新方法,在许多计算和统计指标上都表现出卓越的性能。
与现有技术相比,所提出的算法CaMoDi展示了有效的统计性能,并且算法简单且可扩展——这使其适用于对单个肿瘤以及肿瘤组进行不依赖组织的基因组特征分析。我们在来自癌症基因组图谱的11种单个肿瘤和8种肿瘤组合上,对CaMoDi与之前开发的两种方法(CONEXIC和AMARETTO)进行了广泛的比较研究。我们证明,CaMoDi能够发现具有更好平均一致性和同质性的模块,与CONEXIC和AMARETTO相比,其调整后的R2性能相似或更好。
我们提出了一种用于癌症模块发现的新方法CaMoDi,并通过在TCGA泛癌数据集上进行的广泛模拟证明,它与CONEXIC和AMARETTO相比具有相当或更好的性能,同时与其他方法相比,其计算运行时间提高了一个数量级。