2026-09-21T05:32:18Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/117566 2023-07-11 col_2142_5131 col_2142_8800 com_2142_5130 com_2142_5132

Hudson, Mathew Hudson, Mathew Moose, Stephen Marshall-Colon, Amy Zhao, Sihai 2022-12 application/pdf en text Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2024-12-01 The student, Hans Muller Paul, accepted the attached license on 2022-11-22 at 13:23. The student, Hans Muller Paul, submitted this Dissertation for approval on 2022-11-22 at 13:34. This Dissertation was approved for publication on 2022-11-23 at 08:47. DSpace SAF Submission Ingestion Package generated from Vireo submission #18619 on 2023-04-12 at 11:35:13 Development and application of machine learning tools for the advancement of energy crop genetic manipulation using the CRISPR/Cas technology Muller Paul, Hans 2022-11-23 Machine Learning Crop Sciences Crispr Cas9 Sgrna Algorithm Genome-wide Software Tool Crop genomes, often highly complex and polyploid, are tailored to optimize specific traits by generations of breeding. Editing such genomes without disrupting decades worth of selective breeding is a challenging task. The CRISPR/Cas9 technology's ability to perform targeted mutations has made it a prime candidate for this purpose. The majority of software tools currently available for designing CRISPR/Cas9 guide sequences were developed for mammalian genomes, and focus specifically on the genome's coding regions. We have developed CROPSR | an open-source tool to design and evaluate gRNA sequences for CRISPR experiments. Advantages over competing tools include a genome-wide approach, which facilitates the design of CRISPR/Cas9 guide RNAs in non-coding regions of the genome, and accounts for polyploidy present in many crop genomes. Novel algorithms were developed to increase performance when evaluating crop genomes, but without sacrificing performance when evaluating mammalian genomes. Incorporating biophysical properties of the CRISPR nucleoprotein complex, particularly the secondary structure of the gRNA molecule, enabled a two-fold increase in the correlation between the predicted and experimental metrics for mutation efficiency. Additionally, software performance was optimized to reduce resource allocation and run time. The results presented in this work are the initial steps in a longer journey to improve the tools available editing crop genomes. CROPSR enables a significant reduction in the time needed to design a CRISPR/Cas9 mutation experiments in complex, polyploid genomes. The addition of biophysical characteristics of the CRISPR/Cas9 complex were considered to develop a novel approach for mutation performance evaluation, resulting in significant increases in predictive accuracy and enabling improving confidence in the generated guide sequences. Thesis eng https://hdl.handle.net/2142/117566 Copyright 2022 Hans Müller Paul Ph.D. Dissertation Informatics University of Illinois at Urbana-Champaign Informatics