A mammalian methylation array for profiling methylation levels at conserved sequences.

A mammalian methylation array for profiling methylation levels at conserved sequences.
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哺乳动物甲基化阵列,用于在保守序列上分析甲基化水平。

DOI:
10.1038/s41467-022-28355-z
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发表时间:
2022-02-10
影响因子:
16.6
通讯作者:
Horvath S
Horvath S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arneson A;Haghani A;Thompson MJ;Pellegrini M;Kwon SB;Vu H;Maciejewski E;Yao M;Li CZ;Lu AT;Morselli M;Rubbi L;Barnes B;Hansen KD;Zhou W;Breeze CE;Ernst J;Horvath S

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Infinium甲基化阵列不适用于绝大多数非人类哺乳动物。此外,即使物种特异性阵列可用,它们之间的探针差异也会混淆跨物种比较。为了解决这些挑战,我们开发了哺乳动物甲基化阵列,这是一种单一的定制阵列,可以测量每个物种高达36k个CpG,这些CpG在许多哺乳动物物种中非常保守。我们设计了一组可以耐受特定跨物种突变的探针。我们注释了200多个物种的阵列,并报告了选定物种的CpG岛状态和染色质状态。校准实验证明了在人类、大鼠和小鼠中的高保真度。哺乳动物甲基化阵列有几个优点:它适用于所有哺乳动物物种,甚至那些尚未测序的物种,它提供了保守胞嘧啶的深度覆盖,促进了表观遗传生物标志物的发展,它增加了在一个物种中获得的生物学见解转化为其他物种的可能性。在大多数非人类哺乳动物中探测DNA甲基化的方法缺乏。在这里,作者开发了一种哺乳动物甲基化阵列,其中包括哺乳动物中36k个高度保守的CpG,这将有助于跨物种比较。他们注释了超过200个物种中保守的CpG。该阵列允许测量所有哺乳动物物种中的甲基化,包括未测序的物种。
Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures up to 36k CpGs per species that are well conserved across many mammalian species. We designed a set of probes that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development of epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others. Methods to probe DNA methylation in the majority of non-human mammals are lacking. Here the authors developed a Mammalian Methylation Array that includes 36k well-conserved CpGs in mammals which will facilitate cross-species comparisons. They annotate the conserved CpGs in > 200 species. The array allows one to measure methylation in all mammalian species including unsequenced ones.
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