Reanalysis of Alzheimer's brain sequencing data reveals absence of purported HHV6A and HHV7
Reanalysis of Alzheimer's brain sequencing data reveals absence of purported HHV6A and HHV7
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DOI：
10.1142/s0219720020500122
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发表时间：
2020-02-01
影响因子：
1
通讯作者：
Chorlton, Samuel D.
中科院分区：
文献类型：
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作者：
Chorlton, Samuel D.
Readhead等人最近在Neuron中报道了通过鸟枪测序检测人类疱疹病毒6A（HHV 6A）和7（HHV 7）与阿尔茨海默病的相关性。我对他们改良的Viromescan生物信息学方法的特异性和随后的分析持怀疑态度，原因有很多。使用他们的补充数据，可以计算出天花病毒的流行率，天花病毒是根除疾病天花的病原体，占西奈山脑库数据集的97.5%。Readhead等人的再分析使用高度敏感和特异性的替代方法的数据在他们的样品中没有发现HHV 7读段; HHV 6A读段仅在按报告的HHV 6A丰度排序的前15个样品中的2个中发现。最后，Readhead et al.的改良Viromescan方法确定了其低特异性的原因。
Readhead et al. recently reported in Neuron the detection and association of human herpesviruses 6A (HHV6A) and 7 (HHV7) with Alzheimer's disease by shotgun sequencing. I was skeptical of the specificity of their modified Viromescan bioinformatics method and subsequent analysis for numerous reasons. Using their supplementary data, the prevalence of variola virus, the etiological agent of the eradicated disease smallpox, can be calculated at 97.5% of their Mount Sinai Brain Bank dataset. Reanalysis of Readhead et al.'s data using highly sensitive and specific alternative methods finds no HHV7 reads in their samples; HHV6A reads were found in only 2 out of their top 15 samples sorted by reported HHV6A abundance. Finally, recreation of Readhead et al.'s modified Viromescan method identifies reasons for its low specificity.