“Multi-Tissue Integrative Analysis of Personal Epigenomes”, Joel Rozowsky, Jorg Drenkow, Yucheng T. Yang, Gamze Gursoy, Timur Galeev, Beatrice Borsari, Charles B. Epstein, Kun Xiong, Jinrui Xu, Jiahao Gao, Keyang Yu, Ana Berthel, Zhanlin Chen, Fabio Navarro, Jason Liu, Maxwell S. Sun, James Wright, Justin Chang, Christopher J. F. Cameron, Noam Shoresh, Elizabeth Gaskell, Jessika Adrian, Sergey Aganezov, Gabriela Balderrama-Gutierrez, Samridhi Banskota, Guillermo Barreto Corona, Sora Chee, Surya B. Chhetri, Gabriel Conte Cortez Martins, Cassidy Danyko, Carrie A. Davis, Daniel Farid, Nina P. Farrell, Idan Gabdank, Yoel Gofin, David U. Gorkin, Mengting Gu, Vivian Hecht, Benjamin C. Hitz, Robbyn Issner, Melanie Kirsche, Xiangmeng Kong, Bonita R. Lam, Shantao Li, Bian Li, Tianxiao Li, Xiqi Li, Khine Zin Lin, Ruibang Luo, Mark Mackiewicz, Jill E. Moore, Jonathan Mudge, Nicholas Nelson, Chad Nusbaum, Ioann Popov, Henry E. Pratt, Yunjiang Qiu, Srividya Ramakrishnan, Joe Raymond, Leonidas Salichos, Alexandra Scavelli, Jacob M. Schreiber, Fritz J. Sedlazeck, Lei Hoon See, Rachel M. Sherman, Xu Shi, Minyi Shi, Cricket Alicia Sloan, J. Seth Strattan, Zhen Tan, Forrest Y. Tanaka, Anna Vlasova, Jun Wang, Jonathan Werner, Brian Williams, Min Xu, Chengfei Yan, Lu Yu, Christopher Zaleski, Jing Zhang, J. Michael Cherry, Eric M. Mendenhall, William S. Noble, Zhiping Weng, Morgan E. Levine, Alexander Dobin, Barbara Wold, Ali Mortazavi, Bing Ren, Jesse Gillis, Richard M. Myers, Michael P. Snyder, Jyoti Choudhary, Aleksandar Milosavljevic, Michael C. Schatz, Roderic Guigó, Bradley E. Bernstein, Thomas R. Gingeras, Mark Gerstein2021-04-26 (genome sequencing; similar):
Evaluating 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 4 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-specific 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.