High-throughput DNA methylation profiling using universal bead arrays

Marina Bibikova, Zhenwu Lin, Lixin Zhou, Eugene Chudin, Eliza Wickham Garcia, Bonnie Wu, Dennis Doucet, Neal J. Thomas, Yunhua Wang, Ekkehard Vollmer, Torsten Goldmann, Carola Seifart, Wei Jiang, David L. Barker, Mark S. Chee, Joanna Floros, Jian Bing Fan

Research output: Contribution to journalArticlepeer-review

549 Scopus citations


We have developed a high-throughput method for analyzing the methylation status of hundreds of preselected genes simultaneously and have applied it to the discovery of methylation signatures that distinguish normal from cancer tissue samples. Through an adaptation of the GoldenGate genotyping assay implemented on a BeadArray platform, the methylation state of 1536 specific CpG sites in 371 genes (one to nine CpG sites per gene) was measured in a single reaction by multiplexed genotyping of 200 ng of bisulfite-treated genomic DNA. The assay was used to obtain a quantitative measure of the methylation level at each CpG site. After validating the assay in cell lines and normal tissues, we analyzed a panel of lung cancer biopsy samples (N = 22) and identified a panel of methylation markers that distinguished lung adenocarcinomas from normal lung tissues with high specificity. These markers were validated in a second sample set (N = 24). These results demonstrate the effectiveness of the method for reliably profiling many CpG sites in parallel for the discovery of informative methylation markers. The technology should prove useful for DNA methylation analyses in large populations, with potential application to the classification and diagnosis of a broad range of cancers and other diseases.

Original languageEnglish (US)
Pages (from-to)383-393
Number of pages11
JournalGenome research
Issue number3
StatePublished - Mar 2006

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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