Bin Zhang
Department of Chemistry, Massachusetts Institute of Technology
Predicting three-dimensional genome organization with chromatin states
Abstract: Three-dimensional genome organization is expected to play crucial roles in regulating gene expression and establishing cell fate, and has inspired the development of numerous innovative experimental techniques for its characterization. Though significant progress has been made, it remains challenging to construct chromosome structures at high resolution. Following the maximum entropy approach pioneered by Zhang and Wolynes, we developed a predictive model and parameterized a force field to study chromatin structure and dynamics using genome-wide chromosome conformation capture data (Hi-C). Starting from one-dimensional sequence information that includes histone modification profiles and CTCF binding sites, this model predicts chromosome structure at a 5kb resolution, thus establishing a sequence-structure relationship for the genome. A significant advantage of this model over comparable approaches is its ability to study long-range specific contacts between promoters and enhancers, in addition to building high-resolution structures for loops, TADs and compartments. Furthermore, the model is shown to be transferable across chromosomes and cell types, thus opens up the opportunity to carry out de novo prediction of genome organization for hundreds of cell types with available epigenomics but not Hi-C data.
Abstract: Three-dimensional genome organization is expected to play crucial roles in regulating gene expression and establishing cell fate, and has inspired the development of numerous innovative experimental techniques for its characterization. Though significant progress has been made, it remains challenging to construct chromosome structures at high resolution. Following the maximum entropy approach pioneered by Zhang and Wolynes, we developed a predictive model and parameterized a force field to study chromatin structure and dynamics using genome-wide chromosome conformation capture data (Hi-C). Starting from one-dimensional sequence information that includes histone modification profiles and CTCF binding sites, this model predicts chromosome structure at a 5kb resolution, thus establishing a sequence-structure relationship for the genome. A significant advantage of this model over comparable approaches is its ability to study long-range specific contacts between promoters and enhancers, in addition to building high-resolution structures for loops, TADs and compartments. Furthermore, the model is shown to be transferable across chromosomes and cell types, thus opens up the opportunity to carry out de novo prediction of genome organization for hundreds of cell types with available epigenomics but not Hi-C data.
Biography
Bin Zhang is an assistant professor in the Chemistry department at MIT. He attended the University of Science and Technology of China (USTC) as a chemical physics major, where he developed a strong interest in theoretical chemistry through the undergraduate research program in the group of Jinlong Yang. Bin received numerous awards for his outstanding academic performance, including the prestigious Tang Zhongying Scholarship and the Guo Moruo Scholarship, which is the highest honor for undergraduate students. After graduating from USTC in 2007, Bin moved to the United States to pursue doctoral research at the California Institute of Technology in Thomas Miller’s group. His thesis work on Sec-Facilitated Protein Translocation and Membrane Integration was recognized with the Herbert Newby McCoy Award, the highest award for graduate scientific research from Caltech. Upon graduation, Bin accepted a position as a postdoctoral scholar with Peter G. Wolynes at the Center for Theoretical Biological Physics at Rice University. Bin joined MIT faculty as an assistant professor in 2016. His research focuses on studying three-dimensional genome organization with interdisciplinary approaches that combine bioinformatics analysis, computational modeling and statistical mechanical theory.
Group website
Bin Zhang is an assistant professor in the Chemistry department at MIT. He attended the University of Science and Technology of China (USTC) as a chemical physics major, where he developed a strong interest in theoretical chemistry through the undergraduate research program in the group of Jinlong Yang. Bin received numerous awards for his outstanding academic performance, including the prestigious Tang Zhongying Scholarship and the Guo Moruo Scholarship, which is the highest honor for undergraduate students. After graduating from USTC in 2007, Bin moved to the United States to pursue doctoral research at the California Institute of Technology in Thomas Miller’s group. His thesis work on Sec-Facilitated Protein Translocation and Membrane Integration was recognized with the Herbert Newby McCoy Award, the highest award for graduate scientific research from Caltech. Upon graduation, Bin accepted a position as a postdoctoral scholar with Peter G. Wolynes at the Center for Theoretical Biological Physics at Rice University. Bin joined MIT faculty as an assistant professor in 2016. His research focuses on studying three-dimensional genome organization with interdisciplinary approaches that combine bioinformatics analysis, computational modeling and statistical mechanical theory.
Group website