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         headline:Evaluation of microarray-based DNA methylation measurement using technical replicates: the Atherosclerosis Risk In Communities (ARIC) Study
         description:DNA methylation is a widely studied epigenetic phenomenon; alterations in methylation patterns influence human phenotypes and risk of disease. As part of the Atherosclerosis Risk in Communities (ARIC) study, the Illumina Infinium HumanMethylation450 (HM450) BeadChip was used to measure DNA methylation in peripheral blood obtained from ~3000 African American study participants. Over 480,000 cytosine-guanine (CpG) dinucleotide sites were surveyed on the HM450 BeadChip. To evaluate the impact of technical variation, 265 technical replicates from 130 participants were included in the study. For each CpG site, we calculated the intraclass correlation coefficient (ICC) to compare variation of methylation levels within- and between-replicate pairs, ranging between 0 and 1. We modeled the distribution of ICC as a mixture of censored or truncated normal and normal distributions using an EM algorithm. The CpG sites were clustered into low- and high-reliability groups, according to the calculated posterior probabilities. We also demonstrated the performance of this clustering when applied to a study of association between methylation levels and smoking status of individuals. For the CpG sites showing genome-wide significant association with smoking status, most (~96%) were seen from sites in the high reliability cluster. We suggest that CpG sites with low ICC may be excluded from subsequent association analyses, or extra caution needs to be taken for associations at such sites.
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            Infinium 450 K chip
            Technical error
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            Computer Appl. in Life Sciences
            Algorithms
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      headline:Evaluation of microarray-based DNA methylation measurement using technical replicates: the Atherosclerosis Risk In Communities (ARIC) Study
      description:DNA methylation is a widely studied epigenetic phenomenon; alterations in methylation patterns influence human phenotypes and risk of disease. As part of the Atherosclerosis Risk in Communities (ARIC) study, the Illumina Infinium HumanMethylation450 (HM450) BeadChip was used to measure DNA methylation in peripheral blood obtained from ~3000 African American study participants. Over 480,000 cytosine-guanine (CpG) dinucleotide sites were surveyed on the HM450 BeadChip. To evaluate the impact of technical variation, 265 technical replicates from 130 participants were included in the study. For each CpG site, we calculated the intraclass correlation coefficient (ICC) to compare variation of methylation levels within- and between-replicate pairs, ranging between 0 and 1. We modeled the distribution of ICC as a mixture of censored or truncated normal and normal distributions using an EM algorithm. The CpG sites were clustered into low- and high-reliability groups, according to the calculated posterior probabilities. We also demonstrated the performance of this clustering when applied to a study of association between methylation levels and smoking status of individuals. For the CpG sites showing genome-wide significant association with smoking status, most (~96%) were seen from sites in the high reliability cluster. We suggest that CpG sites with low ICC may be excluded from subsequent association analyses, or extra caution needs to be taken for associations at such sites.
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      dateModified:2014-09-19T00:00:00Z
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         DNA methylation
         Infinium 450 K chip
         Technical error
         Intraclass correlation
         Normal mixture models
         Bioinformatics
         Microarrays
         Computational Biology/Bioinformatics
         Computer Appl. in Life Sciences
         Algorithms
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      name:Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, USA
      name:Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, USA
      name:Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, USA
      name:Department of Neurology and Department of Medicine, University of Mississippi, Jackson, USA
      name:Department of Neurology and Department of Medicine, University of Mississippi, Jackson, USA
      name:Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, USA
      name:Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA
      name:Department of Computer Science, Saint John’s University, Collegeville, USA
      name:Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, USA
      name:Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, USA

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