Zhang, David Yu2019-05-172020-05-012019-052019-04-11May 2019Yan, Yan. "Rationally Designed Hybridization Systems for Nucleic Acid Diagnostics and Sequence Analysis." (2019) Diss., Rice University. <a href="https://hdl.handle.net/1911/105993">https://hdl.handle.net/1911/105993</a>.https://hdl.handle.net/1911/105993Detection of changes in a nucleic acid sequence is crucial in genomics research and precision medicine. With the advances of new generation’s of technology platforms, researchers have been able to study the fundamental causes of human diseases in DNA or RNA level, leading to optimal targeted treatment, real-time monitoring of disease progression, and ultimately early diagnosis and intervention before symptoms occur. Although people have been developing nucleic acid based assays for decades, the common methodology that people use in the design process of nucleic acid based assays are trial and error adjustment of probe or primer sequences and empirical optimization of buffer conditions. These methods offer quantitatively improvements of nucleic acid reaction behaviors (yield and specificity) to a certain degree, but are hard to achieve qualitative breakthroughs. During my PhD, my main focus is how to use the “rational design” concept in nucleic acid technology development. Our lab has an extensive background in nucleic acid hybridization biophysics, which facilitates reliable and generalizable in silico assay and device design with little empirical optimization. As demonstration, 4 technologies have been developed with 4 manuscripts to provide potential solutions for 4 different application fields: 1) DNA signaling and computing device [1] Yan Helen Yan, David Yu Zhang and Lucia R. Wu. “Encoding multiple digital DNA signals in a single analog channel” manuscript in preparation. 2) Hybridization probe [2] Juexiao Sherry Wang*, Yan Helen Yan* and David Yu Zhang. “Modular probes for enriching and detecting complex nucleic acid sequences.” Nature chemistry 9.12 (2017): 1222. *Equal contribution 3) Next generation sequencing [3] Yan Helen Yan and David Yu Zhang. “Symbolic Sequencing of DNA and RNA Via Sequence Encoding.” manuscript in preparation. 4) Quantitative PCR [4] Ping Song, Sherry X. Chen, Yan Helen Yan and David Yu Zhang. “Detecting and Identifying Low Fraction Conspecific DNA” in submission to Nature Methods. These works are not meant to be final, optimized designs for assays and devices, but rather demonstrations of the wide range of problems that can be solved with nucleic acid rational design.application/pdfengCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.DNA biophysicsmolecular diagnosticsprobesThesis2019-05-17