Understanding gene transcriptional regulation at single cell resolution
1 online resource (112 pages) : PDF
University of North Carolina at Charlotte
The recent advance of single-cell technologies has provided an unprecedented opportunity to bring new insights into many complex biological phenomena, such as the regulation of cell differentiation in a multi-cellular organism and cell-to-cell variability in an isogenic population. In this dissertation, we have explored the gene expression regulation using datasets generated by single-cell techniques in three aspects. First, we analyzed a large-scale gene expression dataset measured in individual cells throughout the embryogenesis of C. elegans in a nearly continuous time-scale. We revealed many known and novel genes driving lineage divergence at early cell divisions, facilitating a systematic understanding of the fate specification in C. elegans. Second, we developed a novel clustering algorithm named SNN-Cliq that utilizes the shared nearest neighbor and graph-theoretic partitioning techniques. Our algorithm has the superiority of handling high-dimensional noisy data in that it allows clustering on a variety of single-cell RNA-sequencing (RNA-Seq) data with high accuracy. Last, using an RNA-Seq technique, we profiled transcriptomes in 51 yeast cells from three treatments. Intriguingly, we found that the transcription variation, or noise, shows distinct features under different treatments for certain functional gene modules and regulatory pathways. Our results also suggest that transcriptional noise is subject to regulation in response to environmental stresses. In summary, this dissertation has contributed to algorithmic development for analyzing various single-cell datasets and deepened our knowledge of transcriptional regulation at the single cell level.
CLUSTERINGGENE EXPRESSIONRNA-SEQSINGLE CELLTRANSCRIPTIONAL NOISETRANSCRIPTOME
Guo, Jun-taoWeller, JenniferFodor, AnthonySong, Bao-Hua
Thesis (Ph.D.)--University of North Carolina at Charlotte, 2015.
This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). For additional information, see http://rightsstatements.org/page/InC/1.0/.
Copyright is held by the author unless otherwise indicated.