TY - JOUR T1 - An integrative ENCODE resource for cancer genomics JF - bioRxiv DO - 10.1101/706424 SP - 706424 AU - Jing Zhang AU - Donghoon Lee AU - Vineet Dhiman AU - Peng Jiang AU - Jie Xu AU - Patrick McGillivray AU - Hongbo Yang AU - Jason Liu AU - William Meyerson AU - Declan Clarke AU - Mengting Gu AU - Shantao Li AU - Shaoke Lou AU - Jinrui Xu AU - Lucas Lochovsky AU - Matthew Ung AU - Lijia Ma AU - Shan Yu AU - Qin Cao AU - Arif Harmanci AU - Koon-Kiu Yan AU - Anurag Sethi AU - Gamze Gursoy AU - Michael Rutenberg Schoenberg AU - Joel Rozowsky AU - Jonathan Warrell AU - Prashant Emani AU - Yucheng T. Yang AU - Timur Galeev AU - Xiangmeng Kong AU - Shuang Liu AU - Xiaotong Li AU - Jayanth Krishnan AU - Yanlin Feng AU - Juan Carlos Rivera-Mulia AU - Jessica Adrian AU - James R Broach AU - Michael Bolt AU - Jennifer Moran AU - Dominic Fitzgerald AU - Vishnu Dileep AU - Tingting Liu AU - Shenglin Mei AU - Takayo Sasaki AU - Claudia Trevilla-Garcia AU - Su Wang AU - Yanli Wang AU - Chongzhi Zang AU - Daifeng Wang AU - Robert Klein AU - Michael Snyder AU - David M. Gilbert AU - Kevin Yip AU - Chao Cheng AU - Feng Yue AU - X. Shirley Liu AU - Kevin White AU - Mark Gerstein Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/18/706424.abstract N2 - ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types. A key aspect of this annotation is comprehensive and experimentally derived networks of both transcription factors and RNA-binding proteins (TFs and RBPs). Cancer, a disease of system-wide dysregulation, is an ideal application for such a network-based annotation. Specifically, for cancer-associated cell types, we put regulators into hierarchies and measure their network change (rewiring) during oncogenesis. We also extensively survey TF-RBP crosstalk, highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of MYC, a well-known oncogenic TF. Furthermore, we show how our annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend. Finally, we organize the resource into a coherent workflow to prioritize key elements and variants, in addition to regulators. We showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS. Targeted validations of the prioritized regulators, elements and variants using siRNA knockdowns, CRISPR-based editing, and luciferase assays demonstrate the value of the ENCODE resource. ER -