2023-11-07 オークリッジ国立研究所(ORNL)
◆この研究により、生物工学における強力なツールであるCRISPRのガイドRNA設計を改善し、微生物のゲノム編集が効率的に行えるようになります。このモデルには、量子化学のプロパティも組み込まれ、細胞核でのガイドRNAのDNA結合に対する影響を理解し、最適なガイドRNAを選択するのに役立ちました。
◆この研究は、CRISPR技術の改善と生物学的メカニズムの理解に貢献し、遺伝子型から表現型へのリンクを向上させる重要な一歩です。
<関連情報>
- https://www.ornl.gov/news/scientists-use-quantum-biology-ai-sharpen-genome-editing-tool
- https://academic.oup.com/nar/article/51/19/10147/7279034?login=false
説明可能な AI 主導の特徴エンジニアリングによる CRISPR-Cas9 sgRNA 効率に関する量子生物学的洞察 Quantum biological insights into CRISPR-Cas9 sgRNA efficiency from explainable-AI driven feature engineering
Jaclyn M Noshay, Tyler Walker, William G Alexander, Dawn M Klingeman, Jonathon Romero, Angelica M Walker, Erica Prates, Carrie Eckert, Stephan Irle, David Kainer,Daniel A Jacobson
Nucleic Acids Research Published:20 September 2023
DOI:https://doi.org/10.1093/nar/gkad736
Abstract
CRISPR-Cas9 tools have transformed genetic manipulation capabilities in the laboratory. Empirical rules-of-thumb have been developed for only a narrow range of model organisms, and mechanistic underpinnings for sgRNA efficiency remain poorly understood. This work establishes a novel feature set and new public resource, produced with quantum chemical tensors, for interpreting and predicting sgRNA efficiency. Feature engineering for sgRNA efficiency is performed using an explainable-artificial intelligence model: iterative Random Forest (iRF). By encoding quantitative attributes of position-specific sequences for Escherichia coli sgRNAs, we identify important traits for sgRNA design in bacterial species. Additionally, we show that expanding positional encoding to quantum descriptors of base-pair, dimer, trimer, and tetramer sequences captures intricate interactions in local and neighboring nucleotides of the target DNA. These features highlight variation in CRISPR-Cas9 sgRNA dynamics between E. coli and H. sapiens genomes. These novel encodings of sgRNAs enhance our understanding of the elaborate quantum biological processes involved in CRISPR-Cas9 machinery.
Graphical Abstract
