ORCID ID

0000-0001-7386-8159

Publication Date

2020-11-12

Document Type

Doctoral Dissertation

Academic Program

Bioinformatics and Computational Biology

Department

Bioinformatics and Integrative Biology

First Thesis Advisor

Zhiping Weng

Keywords

bioinformatics, 3D genome, chromatin, TCR-pMHC, protein modeling, Hi-C

Abstract

The 23 pairs of chromosomes comprising the human genome are intricately folded within the nucleus of each cell in a manner that promotes efficient gene regulation and cell function. Consequently, active gene rich regions are compartmentally segregated from inactive gene poor regions of the genome. To better understand the mechanisms driving compartmentalization we investigated what would occur if this system was disrupted. By digesting the genome to varying sizes and analyzing the fragmented 3D structure over time, our work revealed essential laws governing nuclear compartmentalization.

At a finer resolution within compartments, chromatin forms loop structures capable of regulating gene expression. Genome wide association studies have identified numerous single nucleotide polymorphisms (SNPs) associated with the neuropsychiatric disease schizophrenia. When these SNPs are not located within a gene it is difficult to gain insight into disease pathology; however, in some cases chromatin loops may link these noncoding schizophrenia risk variants to their pathological gene targets. By generating 3D genome maps, we identified and analyzed loops of glial cells, neural progenitor cells, and neurons thereby expanding the set of genes conferring schizophrenia risk.

The binding of T-cell receptors (TCRs) to foreign peptides on the surface of diseased cells triggers an immune response against the foreign invader. Utilizing available structural information of the TCR antigen interface, we developed computational methods for successful prediction of TCR-antigen binding. As this binding is a prerequisite for immune response, such improvements in binding prediction could lead to important advancements in the fields of autoimmunity and TCR design for cancer therapeutics.

DOI

10.13028/sh3x-v380

Rights and Permissions

Licensed under a Creative Commons license

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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