@article{THESIS,
      recid = {3663},
      author = {Phan, Hoang Van},
      title = {Simultaneous Quantification of Gene Expression, Protein  and Protein Complex in Single Cells},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2022-03},
      number = {THESIS},
      pages = {192},
      abstract = {Single-cell analysis has become an increasingly important  tool in cell biology. One of the most popular analysis  methods is single-cell ribonucleic acid sequencing  (scRNA-seq), which enables quantification of gene  expression in single cells. This type of information has  led to many important discoveries, from existence of new  cell types to tumor heterogeneity. However, it is proteins,  not RNAs, that are the main effector molecules in  biological processes. Cells recognize environmental signals  using protein receptors on the cell surface. The  environmental signals are then transmitted through protein  interactions inside the cells as part of a signaling  cascade. Finally, the appropriate genes are transcribed,  allowing the cells to respond to the environmental signals.  These protein activities cannot be inferred from gene  expression level alone, because many of them occur prior to  transcription. In this dissertation, we introduce Proximity  sequencing (Prox-seq), a novel single-cell multiomic method  that bridges the gap between gene expression and  protein-protein interactions. Prox-seq combines proximity  ligation assay (PLA) with scRNA-seq to quantify gene  expression level, protein abundance, and most importantly,  protein complexes in the same single cell. First, we  develop Prox-seq for surface receptors, and show that we  can indeed obtain these three types of information from the  same single cells. By applying Prox-seq to peripheral blood  mononuclear cells (PBMCs), we find a putative interaction  between CD8 and CD9 receptors on CD8 T cells. Then, we  develop a high-throughput, droplet-based scRNA-seq for  fixed and permeablized cells, called FD-seq. FD-seq can  serve as a platform to extend Prox-seq to intracellular  proteins. Using FD-seq, we identify host genes that are  associated with herpesvirus reactivation, and show that  following exposure to coronavirus, only a minority of the  cells express a high level of viral genes. Finally, we  develop computational frameworks for simulating Prox-seq  data, and for prediction of protein complexes in single  cells from Prox-seq data.},
      url = {http://knowledge.uchicago.edu/record/3663},
      doi = {https://doi.org/10.6082/uchicago.3663},
}