Umbilical cord blood artificial mixtures validation dataset: An Enhanced DNA Methylation Library for Deconvoluting Peripheral Blood. Umbilical cord blood artificial mixtures validation dataset: An Enhanced DNA Methylation Library for Deconvoluting Peripheral Blood

DNA methylation microarrays have been extensively used for understanding cell type composition in complex tissue samples. Here we expand on existing libraries for reference-based deconvolution of blood DNA methylation data assayed using the Illumina HumanMethylationEPIC array to include 12 different leukocyte subtypes (neutrophils, eosinophils, basophils, monocytes, B cells naïve and memory, CD4+ and CD8+ naïve and memory cells, natural killers, and T regulatory cells). Application of the IDOL algorithm for identifying optimal libraries for the deconvolution of blood-derived DNA methylation data led to to a library consisting of 1200 CpGs. The accuracy of deconvolution estimates obtained using our IDOL-optimized library was evaluated using artificial mixtures with known cellular composition and in samples were both whole-blood DNA methylation data and FACS information were available. We further showcase potential applications of our expanded library using publicly available cancer, aging, and autoimmune disease data sets. Overall design: Bisulphite converted DNA from 12 umbilical cord blood artificial mixtures with six cell types, including CD8T, CD4T, NK, B cell, monocyte, and granulocyte, were hybridised to the Illumina Infinium HumanMethylationEPIC Beadchip v1.0_B4

DNA甲基化微阵列（DNA methylation microarrays）已被广泛应用于解析复杂组织样本中的细胞类型组成。本研究针对采用因美纳（Illumina）HumanMethylationEPIC芯片检测的血液DNA甲基化数据的基于参考的反卷积任务，拓展了现有参考文库，新增纳入12种不同的白细胞亚型：中性粒细胞、嗜酸性粒细胞、嗜碱性粒细胞、单核细胞、初始与记忆性B细胞、CD4阳性及CD8阳性的初始与记忆性细胞、自然杀伤细胞（natural killers，NK）以及调节性T细胞。本研究采用IDOL算法筛选适用于血液来源DNA甲基化数据反卷积的最优参考文库，最终得到包含1200个CpG位点的文库。我们采用已知细胞组成的人工混合样本，以及同时具备全血DNA甲基化数据与荧光激活细胞分选术（Fluorescence-Activated Cell Sorting, FACS）信息的样本，对基于IDOL优化文库的反卷积估计准确性进行了评估。我们还利用公开的癌症、衰老及自身免疫疾病数据集，展示了该拓展文库的潜在应用场景。实验设计方案：将来自12份脐带血人工混合样本的亚硫酸氢盐转化DNA（Bisulphite converted DNA，共包含6种细胞类型：CD8阳性T细胞、CD4阳性T细胞、自然杀伤细胞、B细胞、单核细胞及粒细胞）与因美纳Infinium HumanMethylationEPIC Beadchip v1.0_B4芯片进行杂交。