Computational Biology Thesis Defense

  • Gates Hillman 7501 and Zoom
  • In Person and Virtual ET
  • Ph.D. Student
  • Joint CMU-Pitt Ph.D. Program in Computational Biology
  • Carnegie Mellon University
Thesis Orals

Computational Methods for Integrative Analysis of Nuclear Genome Compartmentalization

In eukaryotic cells, chromosomes are packaged in three-dimensional (3D) nuclear space, which is important for genome functions such as replication and transcription. However, our knowledge of the 3D genome structure remains incomplete. Recent development in high-throughput genome-wide mapping technologies for chromatin interactions has significantly advanced our understanding of the multiscale 3D genome organization. However, it remains unclear how these genome organization features form, what their functional roles are, and how they vary in different cellular conditions. In particular, our knowledge about large-scale nuclear compartmentalization relative to nuclear bodies, which is critical for vital genome functions, is significantly lacking. The overall goal of this Ph.D. dissertation is to make an important step forward to address these questions by developing computational frameworks with a focus on nuclear compartmentalization. Our integrative analysis aims to reveal the variation of nuclear compartmentalization across different cell types and provides a refined understanding on how the 3D genome organization is modulated by information encoded in the genome sequence.

First, I developed the SPIN method to delineate much refined genome-wide chromosome localization patterns relative to multiple nuclear bodies. I then developed enhanced approaches for comparing SPIN states across different cell types. Such comparison of SPIN states across cell types reveals new insights into the variation of nuclear spatial compartmentalization and its functional implications. Finally, I developed approaches for identifying DNA sequences and epigenomic features that collectively modulate nuclear compartmentalization. Overall, the methods developed in this dissertation have provided an integrative solution to the study of spatial localization of large-scale chromatin relative to nuclear bodies. Our analysis also unveils genomic regions with conserved or cell type-specific compartmentalization. Together, this dissertation research is expected to offer novel insights into the principles of nuclear organization and the molecular determinants underpinning the strongly intertwined nature of genome structure and function. 

Thesis Committee:
Jian Ma (Chair, CMU)
Ziv Bar-Joseph (CMU)
Jianhua Xing (PITT)
Frank Alber (University of California, Los Angeles)
Andrew Belmont (University of Illinois, Urbana-Champaign)

In Person and Zoom Participation. See announcement.

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