دورية أكاديمية

Machine learning for design of degenerate Cas13a crRNAs using lassa virus as a model of highly variable RNA target.

التفاصيل البيبلوغرافية
العنوان: Machine learning for design of degenerate Cas13a crRNAs using lassa virus as a model of highly variable RNA target.
المؤلفون: Leski TA; Center for Bio/Molecular Science & Engineering, U.S. Naval Research Laboratory, Washington, USA. tomasz.leski@nrl.navy.mil., Spangler JR; Center for Bio/Molecular Science & Engineering, U.S. Naval Research Laboratory, Washington, USA., Wang Z; Center for Bio/Molecular Science & Engineering, U.S. Naval Research Laboratory, Washington, USA., Schultzhaus Z; Center for Bio/Molecular Science & Engineering, U.S. Naval Research Laboratory, Washington, USA.; U.S. Department of Agriculture, Riverdale, MD, USA., Taitt CR; Center for Bio/Molecular Science & Engineering, U.S. Naval Research Laboratory, Washington, USA.; Nova Research Inc., Alexandria, VA, USA., Dean SN; Center for Bio/Molecular Science & Engineering, U.S. Naval Research Laboratory, Washington, USA., Stenger DA; Center for Bio/Molecular Science & Engineering, U.S. Naval Research Laboratory, Washington, USA.
المصدر: Scientific reports [Sci Rep] 2023 Apr 20; Vol. 13 (1), pp. 6506. Date of Electronic Publication: 2023 Apr 20.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: RNA*/metabolism , Lassa virus*/genetics, RNA Processing, Post-Transcriptional ; CRISPR-Cas Systems/genetics
مستخلص: The design of minimum CRISPR RNA (crRNA) sets for detection of diverse RNA targets using sequence degeneracy has not been systematically addressed. We tested candidate degenerate Cas13a crRNA sets designed for detection of diverse RNA targets (Lassa virus). A decision tree machine learning (ML) algorithm (RuleFit) was applied to define the top attributes that determine the specificity of degenerate crRNAs to elicit collateral nuclease activity. Although the total number of mismatches (0-4) is important, the specificity depends as well on the spacing of mismatches, and their proximity to the 5' end of the spacer. We developed a predictive algorithm for design of candidate degenerate crRNA sets, allowing improved discrimination between "included" and "excluded" groups of related target sequences. A single degenerate crRNA set adhering to these rules detected representatives of all Lassa lineages. Our general ML approach may be applied to the design of degenerate crRNA sets for any CRISPR/Cas system.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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المشرفين على المادة: 63231-63-0 (RNA)
تواريخ الأحداث: Date Created: 20230420 Date Completed: 20230424 Latest Revision: 20230427
رمز التحديث: 20230428
مُعرف محوري في PubMed: PMC10119381
DOI: 10.1038/s41598-023-33494-4
PMID: 37081092
قاعدة البيانات: MEDLINE