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A Study in Genome Editing with Clustered Regularly Interspaced Short Palindromic Repeats

Rostami, Mohammad | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55022 (02)
  4. University: Sharif University of Technology
  5. Department: Mathematical Sciences
  6. Advisor(s): Sharifi Tabar, Mohsen; Rabiee, Hamid Reza; Rohban, Mohammad Hossein
  7. Abstract:
  8. Clustered Regularly Interspaced Short Palindromic Repeats, or in short, CRISPR is a relatively new technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding, or altering parts of the DNA. Initially found in the genomes of prokaryotic organisms such as bacteria and archaea, this technology can cure many illnesses such as blindness and cancer. A significant issue for a practical application of CRISPR systems is accurately predicting the single guide RNA (sgRNA) on-target efficacy and off-target sensitivity. While some methods classify these designs, most algorithms are on separate data with different genes and cells. The lack of generalizability of these methods hinders the use of this guide in clinical trials since, for each treatment, the process must be designed with its unique dataset, which has its own problems. Here we are trying to solve the generalizability of this problem and present general and targeted prediction models that will help researchers optimize the design of sgRNAs with high sensitivity. First, we tackled the problem by leveraging Latent Profile Analysis and attention-based models to combine previous algorithms. However, the results obtained using these methods were not satisfactory since the data was noisy. Finally, we proposed a novel Ensemble Learning method, which is compatible in terms of accuracy. However, our method provides the advantage of generalizability, allowing the model to offer insightful estimates to RNA on-target efficiency that can quickly learn to predict even in new genes or cells
  9. Keywords:
  10. Machine Learning ; Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)System ; Genome Editing ; DNA Breakage ; Deep Learning

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