Zodiac: A Comprehensive Depiction of Genetic Interactions in Cancer by Integrating TCGA Data
Zodiac: A Comprehensive Depiction of Genetic Interactions in Cancer by Integrating TCGA Data
复制标题
DOI：
10.1093/jnci/djv129
复制
发表时间：
2015-08-01
影响因子：
10.3
通讯作者：
Ji, Yuan
中科院分区：
文献类型：
--
作者：
Zhu, Yitan;Xu, Yanxun;Ji, Yuan
背景：遗传相互作用在癌症发展中发挥着关键作用。现有关于癌症遗传相互作用的知识并不完整，特别是缺乏来自大规模癌症基因组数据的证据。癌症基因组图谱 (TCGA) 产生跨基因组学和数千种肿瘤特征的多模式测量，这为研究癌症中基因的相互作用提供了前所未有的机会。方法：我们引入了 Zodiac，一种计算工具和资源，用于将有关癌症遗传相互作用的现有知识与 TCGA 数据中包含的新信息相整合。它是现有知识的演变，将其视为先验图，将其与基于 TCGA 数据的贝叶斯图模型导出的似然模型集成，并生成后验图作为更新和数据增强的知识。简而言之，Zodiac 实现了“先验相互作用图+TCGA 数据 -> 后验相互作用图”。 结果：Zodiac 提供了约 2 亿对基因的分子相互作用。所有结果都是通过大数据分析生成的，并组织成一个允许定制搜索的综合数据库。此外，Zodiac还提供数据处理和分析工具，允许用户定制先前的网络并更新他们感兴趣的遗传途径。 Zodiac 可在 www.compgenome.org/ZODIAC 上公开获取。结论：Zodiac 概括并扩展了癌症分子相互作用的现有知识。它可用于探索癌症中新的基因间相互作用、转录调控和其他类型的分子相互作用。
Background: Genetic interactions play a critical role in cancer development. Existing knowledge about cancer genetic interactions is incomplete, especially lacking evidences derived from large-scale cancer genomics data. The Cancer Genome Atlas (TCGA) produces multimodal measurements across genomics and features of thousands of tumors, which provide an unprecedented opportunity to investigate the interplays of genes in cancer.Methods: We introduce Zodiac, a computational tool and resource to integrate existing knowledge about cancer genetic interactions with new information contained in TCGA data. It is an evolution of existing knowledge by treating it as a prior graph, integrating it with a likelihood model derived by Bayesian graphical model based on TCGA data, and producing a posterior graph as updated and data-enhanced knowledge. In short, Zodiac realizes "Prior interaction map + TCGA data -> Posterior interaction map."Results: Zodiac provides molecular interactions for about 200 million pairs of genes. All the results are generated from a big-data analysis and organized into a comprehensive database allowing customized search. In addition, Zodiac provides data processing and analysis tools that allow users to customize the prior networks and update the genetic pathways of their interest. Zodiac is publicly available at www.compgenome.org/ZODIAC.Conclusions: Zodiac recapitulates and extends existing knowledge of molecular interactions in cancer. It can be used to explore novel gene-gene interactions, transcriptional regulation, and other types of molecular interplays in cancer.