Zodiac: A Comprehensive Depiction of Genetic Interactions in Cancer by Integrating TCGA Data

by Kevin White, Ian T. Foster, Yuan Ji, Zhu Y, Xu Y, Helseth DL Jr, Gulukota K, Yang S, Pesce LL, Mitra R, Müller P, Sengupta S, Guo W, Silverstein JC, Parsad N

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.

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PMID: 25956356