UW Genome Sciences

Research:

Mammalian genome is extensively folded to form complex three-dimensional (3D) chromatin organization to facilitate functional interactions. These 3D structures and functional interactions are dynamics. Understanding these complex functional interactions and their variations will not only advance fundamental biological knowledge, but also provide novel insights into human disease that could lead to new treatment paradigms.
Our research focus on the development and application of advanced genomic technologies to decipher the genome structures, their three-dimensional (3D) organizations and how they modulate molecular phenotypes and complex traits. Our lab pioneered in pair-end-tag (PET) sequencing strategies to advance our ability to understand genome variation and transcription regulation in shaping cellular behavior. In recent years, we developed a suite of approaches including ChIA-PET, ChIA-Drop and ChIATAC to map 3D chromatin conformation which have transformed our understanding in how noncoding elements regulate transcription during development and disease states. We further improved these assays to derive single cell and single molecule resolution for studying complex genome structural variation, specifically, the extrachromosomal DNA (ecDNA) function in cancer. In addition, as one of the pioneers in establishing long-read technologies, we leverage advances in single-molecule, long-read sequencing methods to better identify complex structural variants of ecDNA, their evolution and impacts on ecDNA functions.

• Selected Publications:

Yanfen Zhu, Amit D. Gujar, Chee-Hong Wong, Harianto Tjong, Chew Yee Ngan, Liang Gong, Yi-An Chen, Hoon Kim, Jihe Liu, Meihong Li, Adam Mil-Homens, Rahul Maurya, Chris Kuhlberg, Fanyue Sun, Eunhee Yi, Ana C. deCarvalho, Yijun Ruan, Roel G.W. Verhaak and Chia-Lin Wei. Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription. Cancer Cell (2021) 39(5):694 May 10, doi: 10.1016/j.ccell.2021.03.006.

Ngan CY, Wong CH, Tjong H, Wang W, Goldfeder R, Choi C, He H, Gong L, Lin J, Urban B, Chow J, Li M, Lim J, VPhilip V, Murray SA, Wang H, Wei CL. Chromatin interaction analyses elucidate the roles of PRC2-bound silencers in mouse development. Nat Genet. 2020 Mar;52(3):264-272.

Bertolini JA, Favaro R, Zhu Y, Pagin M, Ngan CY, Wong CH, Tjong H, Vermunt MW, Martynoga B, Barone C, Mariani J, Cardozo MJ, Tabanera N, Zambelli F, Mercurio S, Ottolenghi S, Robson P, Creyghton MP, Bovolenta P, Pavesi G, Guillemot F, Nicolis SK, Wei CL. Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance. Cell Stem Cell.2019. 24(3):462

Meizhen Zheng, Simon Zhongyuan Tian, Daniel Capurso, Minji Kim, Rahul Maurya, Byoungkoo Lee, Emaly Piecuch, Liang Gong, Jacqueline Jufen Zhu, Chee Hong Wong, Chew Yee Ngan, Ping Wang, Xiaoan Ruan, Chia-Lin Wei, Yijun Ruan. Multiplex Chromatin Interaction Analysis by Droplet Sequencing with Single Molecule Precision. Nature. 2019 Feb;566(7745):558-562.

Haoxi Chai, Harianto Tjong, Peng Li, Wei Liao, Ping Wang, Chee Hong Wong, Chew Yee Ngan, Warren J Leonard, Chia-Lin Wei, Yijun Ruan. ChIATAC is an efficient strategy for multi-omics mapping of 3D epigenomes from low-cell inputs. Nat. Comm. 2023 14(1):213.

Liang Gong, Chee-Hong Wong, Wei-Chung Cheng, Harianto Tjong, Francesca Menghi, Chew Yee Ngan, Edison T. Liu, Chia-Lin Wei (2018). Picky Comprehensively Detects High Resolution Structural Variants in Nanopore Long Reads. Nature Methods 15 (6), 455-460. doi: 10.1038/s41592-018-0002-6

Zhang Y, Wong CH, Birnbaum RY, Li G, Favaro R, Ngan CY, Lim J, Tai E, Poh HM, Wong E, Mulawadi FH, Sung WK, Nicolis S, Ahituv N, Ruan Y, Wei CL. Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations. Nature. 2013 Dec 12;504(7479):306-10.