Description:

The Department of Biochemistry & Molecular Genetics presents:

Aristotelis Tsirigos, PhD
Professor of Medicine and Pathology
Co-director, Precision Medicine
Director, Applied Bioinformatics Laboratories
NYU Grossman School of Medicine

Presentation:

"Deciphering the 3D chromatin landscape in acute leukemia using data integration and machine learning”

Abstract:

The way chromatin is organized in three dimensions can affect the integrity of specific regions known as topologically associating domains (TADs), and modify interactions between enhancers and promoters, which ultimately impacts gene expression and can contribute to human diseases. We investigated the three-dimensional chromatin architecture in acute lymphoblastic leukemia (ALL) using patient samples and observed how the 3D genome architecture is remodeled in leukemia. By examining multiple sets of data, including in situ Hi-C, RNA-seq, and CTCF ChIP-seq, we discovered widespread differences in chromatin interactions within TADs and the insulation of TAD boundaries in ALL. Additionally, our data shows that small-molecule inhibitors that target oncogenic signal transduction or epigenetic regulation can change specific 3D interactions found. Overall, our genomics studies highlight how complex and dynamic three-dimensional chromatin architecture can impact human acute leukemia. Finally, we discuss C.Origami, a transformed-based deep learning architecture that predicts 3D architecture based on DNA sequence, chromatin accessibility and CTCF binding. Using C.Origami, we performed a series of in silico experiments to not only predict chromatin structure, but to also identify cell-type-specific regulatory elements as well as regulators in leukemia. 

Host: Dr. Feng Yue, Professor of Biochemistry and Molecular Genetics