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DNA methylation signatures to predict the cervicovaginal microbiome status
Clinical Epigenetics ( IF 5.7 ) Pub Date : 2020-11-23 , DOI: 10.1186/s13148-020-00966-7
Nuno R Nené 1, 2 , James Barrett 1, 3, 4 , Allison Jones 1 , Iona Evans 1 , Daniel Reisel 1 , John F Timms 1 , Tobias Paprotka 5 , Andreas Leimbach 5 , Dorella Franchi 6 , Nicoletta Colombo 6, 7 , Line Bjørge 8, 9 , Michal Zikan 10, 11 , David Cibula 11 , Martin Widschwendter 1, 3, 4
Affiliation  

The composition of the microbiome plays an important role in human health and disease. Whether there is a direct association between the cervicovaginal microbiome and the host’s epigenome is largely unexplored. Here we analyzed a total of 448 cervicovaginal smear samples and studied both the DNA methylome of the host and the microbiome using the Illumina EPIC array and next-generation sequencing, respectively. We found that those CpGs that are hypo-methylated in samples with non-lactobacilli (O-type) dominating communities are strongly associated with gastrointestinal differentiation and that a signature consisting of 819 CpGs was able to discriminate lactobacilli-dominating (L-type) from O-type samples with an area under the receiver operator characteristic curve (AUC) of 0.84 (95% CI = 0.77–0.90) in an independent validation set. The performance found in samples with more than 50% epithelial cells was further improved (AUC 0.87) and in women younger than 50 years of age was even higher (AUC 0.91). In a subset of 96 women, the buccal but not the blood cell DNA showed the same trend as the cervicovaginal samples in discriminating women with L- from O-type cervicovaginal communities. These findings strongly support the view that the epithelial epigenome plays an essential role in hosting specific microbial communities.

中文翻译:

预测宫颈阴道微生物组状态的 DNA 甲基化特征

微生物组的组成在人类健康和疾病中起着重要作用。宫颈阴道微生物组与宿主的表观基因组之间是否存在直接关联在很大程度上尚未得到探索。在这里,我们分析了总共 448 个宫颈阴道涂片样本,并分别使用 Illumina EPIC 阵列和下一代测序研究了宿主的 DNA 甲基化组和微生物组。我们发现,在具有非乳酸杆菌(O 型)优势群落的样本中那些低甲基化的 CpG 与胃肠道分化密切相关,并且由 819 个 CpG 组成的特征能够区分乳酸杆菌优势(L 型)与胃肠道分化。 O 型样本在独立验证集中的接受者操作特征曲线 (AUC) 下面积为 0.84(95% CI = 0.77–0.90)。在具有超过 50% 上皮细胞的样本中发现的性能进一步提高 (AUC 0.87),并且在 50 岁以下的女性中甚至更高 (AUC 0.91)。在 96 名女性的一个子集中,在区分 L- 女性与 O 型宫颈阴道社区方面,颊部而非血细胞 DNA 显示出与宫颈阴道样本相同的趋势。这些发现强烈支持上皮表观基因组在承载特定微生物群落中发挥重要作用的观点。
更新日期:2020-11-23
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