Author:
Rozowsky Joel,Drenkow Jorg,Yang Yucheng T,Gursoy Gamze,Galeev Timur,Borsari Beatrice,Epstein Charles B,Xiong Kun,Xu Jinrui,Gao Jiahao,Yu Keyang,Berthel Ana,Chen Zhanlin,Navarro Fabio,Liu Jason,Sun Maxwell S,Wright James,Chang Justin,Cameron Christopher JF,Shoresh Noam,Gaskell Elizabeth,Adrian Jessika,Aganezov Sergey,Balderrama-Gutierrez Gabriela,Banskota Samridhi,Corona Guillermo Barreto,Chee Sora,Chhetri Surya B,Cortez Martins Gabriel Conte,Danyko Cassidy,Davis Carrie A,Farid Daniel,Farrell Nina P,Gabdank Idan,Gofin Yoel,Gorkin David U,Gu Mengting,Hecht Vivian,Hitz Benjamin C,Issner Robbyn,Kirsche Melanie,Kong Xiangmeng,Lam Bonita R,Li Shantao,Li Bian,Li Tianxiao,Li Xiqi,Lin Khine Zin,Luo Ruibang,Mackiewicz Mark,Moore Jill E,Mudge Jonathan,Nelson Nicholas,Nusbaum Chad,Popov Ioann,Pratt Henry E,Qiu Yunjiang,Ramakrishnan Srividya,Raymond Joe,Salichos Leonidas,Scavelli Alexandra,Schreiber Jacob M,Sedlazeck Fritz J,See Lei Hoon,Sherman Rachel M,Shi Xu,Shi Minyi,Sloan Cricket Alicia,Strattan J Seth,Tan Zhen,Tanaka Forrest Y,Vlasova Anna,Wang Jun,Werner Jonathan,Williams Brian,Xu Min,Yan Chengfei,Yu Lu,Zaleski Christopher,Zhang Jing,Cherry J Michael,Mendenhall Eric M,Noble William S,Weng Zhiping,Levine Morgan E,Dobin Alexander,Wold Barbara,Mortazavi Ali,Ren Bing,Gillis Jesse,Myers Richard M,Snyder Michael P,Choudhary Jyoti,Milosavljevic Aleksandar,Schatz Michael C,Guigó Roderic,Bernstein Bradley E,Gingeras Thomas R,Gerstein Mark
Abstract
AbstractEvaluating the impact of genetic variants on transcriptional regulation is a central goal in biological science that has been constrained by reliance on a single reference genome. To address this, we constructed phased, diploid genomes for four cadaveric donors (using long-read sequencing) and systematically charted noncoding regulatory elements and transcriptional activity across more than 25 tissues from these donors. Integrative analysis revealed over a million variants with allele-specific activity, coordinated, locus-scale allelic imbalances, and structural variants impacting proximal chromatin structure. We relate the personal genome analysis to the ENCODE encyclopedia, annotating allele- and tissue-specific elements that are strongly enriched for variants impacting expression and disease phenotypes. These experimental and statistical approaches, and the corresponding EN-TEx resource, provide a framework for personalized functional genomics.
Publisher
Cold Spring Harbor Laboratory