Buffy Coat DNA Methylation Profile Is Representative of Methylation Patterns in White Blood Cell Types in Normal Pregnancy.
Buffy Coat DNA Methylation Profile Is Representative of Methylation Patterns in White Blood Cell Types in Normal Pregnancy.
复制标题
DOI：
10.3389/fbioe.2021.782843
复制
发表时间：
2021
影响因子：
5.7
通讯作者：
Garovic VD
中科院分区：
文献类型：
--
作者：
Ghamrawi R;Velickovic I;Milicevic O;White WM;Thistlethwaite LR;Cunningham JM;Milosavljevic A;Milic NM;Garovic VD
背景资料：我们的目的是评估血沉棕黄层DNA甲基化组在多大程度上代表了正常妊娠中组成型白色血细胞（WBC）类型的甲基化模式。 研究方法：比较血沉棕黄层DNA与从多形核白细胞（PMN）和淋巴细胞组分中分离的DNA的差异甲基化，对29名血压正常的孕妇分娩前24小时内获得的每个血液样本进行。使用Illumina Human Methylation 450 BeadChip和CHaMP生物信息学管道获得甲基化谱。使用统计建模和富集分析进一步研究了显示不一致甲基化的差异甲基化探针（DMP）的子集。 结果：在血沉棕黄层和中性粒细胞之间DMPs的数量最少（2.96%）。DMP的途径富集分析鉴定了涉及特定白细胞谱系的生物途径，与分离期间的扰动一致。使用线性模型将血沉棕黄层和分离的级分作为一组进行比较，得到少量具有不一致甲基化的探针（129，000）。与衍生细胞系相比，血沉棕黄层中探针的去甲基化更常见，并且在大陆架和公海区域普遍存在。 结论：血沉棕黄层是正常妊娠白细胞类型甲基化模式的代表。差异甲基化与组分细胞分离期间的扰动一致，并且可能源于体外，这是由于细胞分离期间的物理应力，并且没有生理相关性。这些发现有助于解释怀孕和许多其他情况下的DNA甲基化谱。
Background: We aimed to assess the extent to which the buffy coat DNA methylome is representative of methylation patterns in constitutive white blood cell (WBC) types in normal pregnancy. Methods: A comparison of differential methylation of buffy coat DNA vs DNA isolated from polymorphonuclear (PMN) and lymphocytic fractions was performed for each blood sample obtained within 24 h prior to delivery from 29 normotensive pregnant women. Methylation profiles were obtained using an Illumina Human Methylation 450 BeadChip and CHaMP bioinformatics pipeline. A subset of differentially methylated probes (DMPs) showing discordant methylation were further investigated using statistical modeling and enrichment analysis. Results: The smallest number of DMPs was found between the buffy coat and the PMN fraction (2.96%). Pathway enrichment analysis of the DMPs identified biological pathways involved in the particular leukocyte lineage, consistent with perturbations during isolation. The comparisons between the buffy coat and the isolated fractions as a group using linear modeling yielded a small number of probes (∼29,000) with discordant methylation. Demethylation of probes in the buffy coat compared to derived cell lines was more common and was prevalent in shelf and open sea regions. Conclusion: Buffy coat is representative of methylation patterns in WBC types in normal pregnancy. The differential methylations are consistent with perturbations during isolation of constituent cells and likely originate in vitro due to the physical stress during cell separation and are of no physiological relevance. These findings help the interpretation of DNA methylation profiling in pregnancy and numerous other conditions.
登录
查看更多内容
从头开始鉴定人基因组中差异甲基化区域。
影响因子：
3.9
作者：
Peters TJ;Buckley MJ;Statham AL;Pidsley R;Samaras K;V Lord R;Clark SJ;Molloy PL
通讯作者：
Molloy PL
影响因子：
8.8
作者：
Onuchic V;Hartmaier RJ;Boone DN;Samuels ML;Patel RY;White WM;Garovic VD;Oesterreich S;Roth ME;Lee AV;Milosavljevic A
通讯作者：
Milosavljevic A
影响因子：
3.7
作者：
Dou, John;Schmidt, Rebecca J.;Bakulski, Kelly M.
通讯作者：
Bakulski, Kelly M.
影响因子：
5.8
作者：
Geeleher, Paul;Hartnett, Lori;Seoighe, Cathal
通讯作者：
Seoighe, Cathal
影响因子：
56.9
作者：
Hellman, Asaf;Chess, Andrew
通讯作者：
Chess, Andrew