Ali Mertcan Kose, Ozan Kocadagli, Cihan Taştan, Cagdas Aktan, Onur Mert Ünaldı, Elanur Güzenge, Hamza Emir Erdil
{"title":"Unveiling Off-Target Mutations in CRISPR Guide RNAs: Implications for Gene Region Specificity.","authors":"Ali Mertcan Kose, Ozan Kocadagli, Cihan Taştan, Cagdas Aktan, Onur Mert Ünaldı, Elanur Güzenge, Hamza Emir Erdil","doi":"10.1089/crispr.2024.0002","DOIUrl":null,"url":null,"abstract":"<p><p>The revolutionary CRISPR-Cas9 technology has revolutionized genetic engineering, and it holds immense potential for therapeutic interventions. However, the presence of off-target mutations and mismatch capacity poses significant challenges to its safe and precise implementation. In this study, we explore the implications of off-target effects on critical gene regions, including exons, introns, and intergenic regions. Leveraging a benchmark dataset and using innovative data preprocessing techniques, we have put forth the advantages of categorical encoding over one-hot encoding in training machine learning classifiers. Crucially, we use latent class analysis (LCA) to uncover subclasses within the off-target range, revealing distinct patterns of gene region disruption. Our comprehensive approach not only highlights the critical role of model complexity in CRISPR applications but also offers a transformative off-target scoring procedure based on ML classifiers and LCA. By bridging the gap between traditional target-off scoring and comprehensive model analysis, our study advances the understanding of off-target effects and opens new avenues for precision genome editing in diverse biological contexts. This work represents a crucial step toward ensuring the safety and efficacy of CRISPR-based therapies, underscoring the importance of responsible genetic manipulation for future therapeutic applications.</p>","PeriodicalId":54232,"journal":{"name":"CRISPR Journal","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CRISPR Journal","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/crispr.2024.0002","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
The revolutionary CRISPR-Cas9 technology has revolutionized genetic engineering, and it holds immense potential for therapeutic interventions. However, the presence of off-target mutations and mismatch capacity poses significant challenges to its safe and precise implementation. In this study, we explore the implications of off-target effects on critical gene regions, including exons, introns, and intergenic regions. Leveraging a benchmark dataset and using innovative data preprocessing techniques, we have put forth the advantages of categorical encoding over one-hot encoding in training machine learning classifiers. Crucially, we use latent class analysis (LCA) to uncover subclasses within the off-target range, revealing distinct patterns of gene region disruption. Our comprehensive approach not only highlights the critical role of model complexity in CRISPR applications but also offers a transformative off-target scoring procedure based on ML classifiers and LCA. By bridging the gap between traditional target-off scoring and comprehensive model analysis, our study advances the understanding of off-target effects and opens new avenues for precision genome editing in diverse biological contexts. This work represents a crucial step toward ensuring the safety and efficacy of CRISPR-based therapies, underscoring the importance of responsible genetic manipulation for future therapeutic applications.
CRISPR JournalBiochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
6.30
自引率
2.70%
发文量
76
期刊介绍:
In recognition of this extraordinary scientific and technological era, Mary Ann Liebert, Inc., publishers recently announced the creation of The CRISPR Journal -- an international, multidisciplinary peer-reviewed journal publishing outstanding research on the myriad applications and underlying technology of CRISPR.
Debuting in 2018, The CRISPR Journal will be published online and in print with flexible open access options, providing a high-profile venue for groundbreaking research, as well as lively and provocative commentary, analysis, and debate. The CRISPR Journal adds an exciting and dynamic component to the Mary Ann Liebert, Inc. portfolio, which includes GEN (Genetic Engineering & Biotechnology News) and more than 80 leading peer-reviewed journals.