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.

中文翻译：

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对阿尔茨海默氏症大脑测序数据的重新分析显示缺乏所谓的 HHV6A 和 HHV7

读数头等人。最近在 Neuron 上报道了通过鸟枪测序检测人类疱疹病毒 6A (HHV6A) 和 7 (HHV7) 与阿尔茨海默病的关联。由于多种原因，我对他们改进的 Viromescan 生物信息学方法和后续分析的特异性持怀疑态度。使用他们的补充数据，可以在他们的西奈山脑库数据集的 97.5% 处计算出天花病毒（天花被根除的病原体）的流行率。使用高度敏感和特定的替代方法对 Readhead 等人的数据进行再分析，发现他们的样本中没有 HHV7 读数；在按报告的 HHV6A 丰度排序的前 15 个样本中，仅在 2 个中发现了 HHV6A 读数。最后，重新创建 Readhead 等人的修改后的 Viromescan 方法确定了其低特异性的原因。