Unveiling Off-Target Mutations in CRISPR Guide RNAs: Implications for Gene Region Specificity

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dc.authorid0000-0003-4354-7383en_US
dc.contributor.authorKöse, Ali Mertcan
dc.contributor.authorKocadağlı, Ozan
dc.contributor.authorTaştan, Cihan
dc.contributor.authorAktan, Çağdaş
dc.contributor.authorÜnaldı, Onur Mert
dc.contributor.authorGüzenge, Elanur
dc.contributor.authorErdil, Hamza Emir
dc.date.accessioned2024-07-16T12:15:50Z
dc.date.available2024-07-16T12:15:50Z
dc.date.issued2024en_US
dc.departmentMeslek Yüksekokulları, Meslek Yüksek Okulu, Bilgisayar Teknolojileri Bölümüen_US
dc.description.abstractThe 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.en_US
dc.identifier.doi10.1089/crispr.2024.0002en_US
dc.identifier.endpage178en_US
dc.identifier.issue3en_US
dc.identifier.pmid38922052en_US
dc.identifier.scopus2-s2.0-85197431070en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage168en_US
dc.identifier.urihttps://hdl.handle.net/11467/7343
dc.identifier.urihttps://doi.org/10.1089/crispr.2024.0002
dc.identifier.volume7en_US
dc.identifier.wosWOS:001254879300003en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherMary Ann Liebert Inc.en_US
dc.relation.ispartofCRISPR Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleUnveiling Off-Target Mutations in CRISPR Guide RNAs: Implications for Gene Region Specificityen_US
dc.typeArticleen_US

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