通过深度测序改善了对宿主内部低频变异的检测:人类乳头瘤病毒的案例研究
Sambit K Mishra1,2, Chase W Nelson1, Bin Zhu1
1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 9609 Medical Center Drive, Rockville, MD 20850, USA.
Virus evolution
|March 8, 2024
概括
人类乳头瘤病毒 (HPV) 研究中的测序错误可以与真正的肠内单核酸变异 (iSNVs) 区分开来. 新的方法,VCFgenie和机器学习,在主机内部分析中改进了iSNV检测.
科学领域:
- 基因组学就是基因组学.
- 病毒学 病毒学
- 生物信息学是一种生物信息学.
背景情况:
- 高覆盖度测序可以检测低频变体,但容易发生测序错误.
- 人类乳头瘤病毒 (HPV) 全基因组测序通常使用Ion Torrent,以低单核酸变体 (SNV) 错误率而闻名.
- 由于其独特的生命周期,在HPV中对肠内SNV (iSNV) 进行基准测试是困难的.
研究的目的:
- 在HPV18深度测序数据中区分测序错误与真实iSNV.
- 开发和评估用于准确检测iSNV的新型计算方法.
- 在病毒测序研究中提高宿主变异分析的可靠性.
主要方法:
- 在三个复制品中对31个HPV18样本进行深度测序.
- 基于复制一致性和三核酸背景的SNV模式的分析.
- 开发VCFgenie (动态二项过) 和一个机器学习分类器 (eXtreme梯度提升).
主要成果:
- 测序错误主要是C→T变化,无论三核酸背景如何.
- 真正的iSNV表现出不同的模式,在CCG环境中C→T率高,在ACG环境中C→A率高.
- 无论是VCFgenie还是机器学习分类器,都表现优于固定截止线过,组合使用带来了更高的性能.
结论:
- 真正的iSNV的表征为改进的检测方法提供了基础.
- 与传统方法相比,VCFgenie和机器学习为识别iSNV提供了更高的准确性.
- 这些发现有助于在测序平台上准确检测宿主内病毒变异.
相关概念视频
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:26Human Virome
The human body harbors a vast and diverse viral community known as the human virome. The virome includes bacteriophages that infect bacteria, and eukaryotic viruses that infect human cells. Transient dietary and environmental viruses also contribute to this dynamic ecosystem. Estimates suggest the human body may contain on the order of 10¹³ viral particles, though abundance varies widely by body site and detection method.Comprehensive characterization of the virome has become possible only with...