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一种基于基因表达的计算模型的CRISPR-Cas9 sgRNA评估工具

Shai Cohen¹, Shaked Bergman¹, Nicolas Lynn¹

¹Department of Biomedical Engineering, Tel Aviv University, Tel-Aviv, 6997801, Israel.

Genome medicine

|December 23, 2024

概括

EXPosition是一个新的工具,通过整合基因表达来预测CRISPR基因淘汰,提高了对现有方法的准确性. 它预测转录,拼接和翻译,以获得更好的基因组编辑结果.

科学领域:

基因组学就是基因组学.
分子生物学分子生物学
生物信息学是一种生物信息学.

背景情况:

克里斯普尔基因沉默依赖于突变,但往往忽略了基因表达的影响.
现有的工具可以预测CRISPR的淘汰,但缺少基因表达分析.
准确预测CRISPR结果需要整合基因表达数据.

研究的目的:

开发一个计算工具,EXPosition,通过结合基因表达来预测CRISPR结果.
为了提高CRISPR诱导基因淘汰预测的准确性.
提供一种帮助基因组编辑项目的效率和成功的工具.

主要方法:

开发了EXPosition,这是一种结合淘汰和基因表达预测模型的新型计算工具.
利用深度学习来模拟转录,拼接和翻译启动.
使用6个数据集,4种细胞类型和约207k个sgRNA以及ClinVar数据集验证的模型.

主要成果:

在不同数据集和细胞类型的基因淘汰预测方面,EXPosition的性能优于现有的工具.
深度学习模型准确地预测了关键的基因表达步骤.
基因表达模型显示在ClinVar数据中的高得分突变中致病突变的丰富.

结论:

通过预测CRISPR对基因表达的影响,EXPosition提高了基因组编辑的效率和准确性.
该工具可以更好地预测CRISPR诱导的基因沉默.
EXPosition 是公开可用于研究的.

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CRISPR

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...

CRISPR and crRNAs

CRISPR and crRNAs

Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...