DNA methylation arrays as surrogate measures of cell mixture distribution.
DNA methylation arrays as surrogate measures of cell mixture distribution.
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DOI：
10.1186/1471-2105-13-86
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发表时间：
2012-05-08
影响因子：
3
通讯作者：
Kelsey KT
中科院分区：
文献类型：
--
作者：
Houseman EA;Accomando WP;Koestler DC;Christensen BC;Marsit CJ;Nelson HH;Wiencke JK;Kelsey KT
生物医学研究长期以来一直需要一种能够量化白细胞正常混合成分的方法，而这种方法超出了简单的组织学或流式细胞术评估所能达到的范围。后者受到蛋白质表位的不稳定性质、细胞处理要求和及时细胞分析的限制。在多种疾病中以及在多次免疫毒性暴露后，白细胞组成将为大多数慢性疾病的基础免疫生物学提供重要信息。新兴研究表明，DNA 甲基化负责细胞分化，在全外周血中进行测量时，可用于区分癌症病例和对照。在这里，我们提出了一种类似于回归校准的方法，用于使用 DNA 甲基化特征结合先前获得的由纯化白细胞样本的特征组成的外部验证集来推断不同亚群（例如病例和对照）之间白细胞分布的变化。我们在细胞混合物重建实验中验证了基本思想，然后在多项研究的 DNA 甲基化数据集上展示了我们的方法，包括来自头颈鳞状细胞癌 (HNSCC) 研究和卵巢癌研究的数据。我们的方法产生的结果与先前的生物学发现一致，从而验证了该方法。我们的方法与适当的外部验证集相结合，为疾病状态和有害暴露的大规模免疫学研究带来了新的机会。
There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls. Here we present a method, similar to regression calibration, for inferring changes in the distribution of white blood cells between different subpopulations (e.g. cases and controls) using DNA methylation signatures, in combination with a previously obtained external validation set consisting of signatures from purified leukocyte samples. We validate the fundamental idea in a cell mixture reconstruction experiment, then demonstrate our method on DNA methylation data sets from several studies, including data from a Head and Neck Squamous Cell Carcinoma (HNSCC) study and an ovarian cancer study. Our method produces results consistent with prior biological findings, thereby validating the approach. Our method, in combination with an appropriate external validation set, promises new opportunities for large-scale immunological studies of both disease states and noxious exposures.
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影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E
影响因子：
11.5
作者：
Kuss, I;Hathaway, B;Whiteside, TL
通讯作者：
Whiteside, TL
通过替代变量分析捕获基因表达研究中的异质性。
影响因子：
4.5
作者：
Leek, Jeffrey T.;Storey, John D.
通讯作者：
Storey, John D.
影响因子：
4.5
作者：
Kerkel K;Schupf N;Hatta K;Pang D;Salas M;Kratz A;Minden M;Murty V;Zigman WB;Mayeux RP;Jenkins EC;Torkamani A;Schork NJ;Silverman W;Croy BA;Tycko B
通讯作者：
Tycko B
影响因子：
3.2
作者：
Gaujoux, Renaud;Seoighe, Cathal
通讯作者：
Seoighe, Cathal