Mammalian Evolution of Human cis-regulatory Elements and Transcription Factor Binding Sites
Monday, May 1, 2023 - 4:15pm
Icahn 101
Quantitative & Computational Biology
LSI - Genomics

Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using 241 mammalian genomes recently sequenced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.6 million human transcription factor binding sites (TFBSs). We identified 439,461 cCREs and 2,024,062 TFBSs under evolutionary constraint. Genes near constrained elements perform fundamental cellular processes, while genes near primate-specific elements are involved in environmental interaction, including odor perception and immune response. About 20% of TFBSs are transposable element-derived and exhibit intricate patterns of gains and losses during primate evolution, while sequence variants associated with complex traits are enriched in constrained TFBSs. Our annotations illuminate the regulatory functions of the human genome.

Zhipeng Weng

Dr. Zhiping Weng is the Li Weibo Chair in Biomedical Research and a Professor of Biochemistry and Molecular Biotechnology at the University of Massachusetts Chan Medical School. She is the founding Director of the Program in Bioinformatics and Integrative Biology, overseeing research, education, and professional development for faculty, students, and staff. Dr. Weng received her B.S. in Electrical Engineering from the University of Science and Technology of China in 1992 and completed her Ph.D. in Biomedical Engineering at Boston University in 1997.

Dr. Weng’s research interests center on genomics, epigenomics, transcriptomics, and molecular recognition in biomedical investigations. Her laboratory leverages advanced computational and statistical methods to study biological problems that involve large amounts of data, such as gene regulation by transcriptional and post-transcriptional mechanisms, as well as protein-protein interactions. Dr. Weng has developed a systematic approach to identify regulatory elements in the human and mouse genomes using a select set of predictive epigenetic signals. Her lab also annotates the activities of these elements across hundreds of cell and tissue types. Additionally, her lab has created a powerful software-engineering platform that enables biomedical and clinical scientists to investigate individual elements and their various annotations, including the genetic variations associated with human diseases. Through close collaboration with experimental labs at UMass Chan, her lab has also significantly contributed to unraveling the biogenesis and functions of small silencing RNAs.

Dr. Weng is a well-established leader in large-scale epigenomic sciences. From 2012 to 2022, she served as the leader of the Data Analysis Center for the ENCODE Consortium, and since 2015, she has co-led the Data Analysis Center for the psychENCODE Consortium. These two consortia aim to investigate the regulatory landscapes in the human genome, with ENCODE focusing on normal physiology and psychENCODE on psychiatric disorders. As a leading computational genomicist, Dr. Weng represents the next generation of researchers who utilize the power of computing on big data to unravel the mysteries of the human genome.

Dr. Weng has published over 250 scientific papers published to date. Her work has been cited over 70,000 times, and her H-index is 111 as of April 2023. She has been recognized with various awards, including a Professional Opportunities for Women award from the National Science Foundation in 1998 and a CAREER Award in 2002. In 2013, Dr. Weng was elected a Fellow of the American Institute for Medical and Biological Engineering, and in 2020, she was elected a Fellow of the International Society of Computational Biology. In 2018, UMass Medical School awarded her the Li Weibo Chair in Biomedical Research. Dr. Weng also co-founded Rgenta, a biotech startup in MA that focuses on developing small molecule therapeutics and directs its Scientific Advisory Board. In recognition of her exceptional contributions to the field, she was awarded the 2022 Charles DeLisi Award in the College of Engineering at Boston University.